Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06322186
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-20
First Post:
2024-02-01
Brief Title:
Study to Actively Warm Trauma Patients-2
Sponsor:
Sunnybrook Health Sciences Centre
Organization:
Sunnybrook Health Sciences Centre
Study Overview
Official Title:
Study to Actively Warm Trauma Patients-2 STAYWARM-2 A Pilot Feasibility Trial of Chemical Versus Passive Warming Blankets in Massively Bleeding Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
STAYWARM-2
Brief Summary:
Massively bleeding trauma patients have higher odds of mortality increased hospital length of stay and increased need for transfusion if they become hypothermic Hypothermia is independently associated with mortality in traumatically injured patients due to its negative physiologic effects on hemostasis cardiorespiratory and renal function
Current warming strategies increase the logistical difficulty of transferring patients which is frequent during the initial hours of trauma care or must be changed at frequent intervals Prehospital military and intraoperative studies have suggested chemical warming blankets as a pragmatic strategy to manage hypothermia A recent pilot study manuscript under review at our institution demonstrated the feasibility of using the Ready-Heat TechTrade LLC Orlando FL USA chemical heating blanket in the initial phases of hospital care in bleeding trauma patients requiring a mass hemorrhage protocol MHP These self-warming blankets provide warmth over 8 hours at up to 40 degrees Celsius carrying the advantage of portability with no continuous electric power requirement Furthermore the Ready-Heat blanket may be more effective than current strategies for rewarming patients at high risk of developing hypothermia STAYWARM-2 will be the first randomized controlled trial performed in-hospital to evaluate a self-warming blanket to address hypothermia in massively bleeding trauma patients within the initial hours of hospital arrival
This study will help to determine the efficacy and feasibility of using chemical heating blankets for hypothermia in the early hours of hospital care This has potential to reduce the overall workload of direct care clinicians freeing them for other patient care duties Additionally the intervention may achieve enhanced thermoregulation compared to current strategies improving patient care and comfort and avoiding the clinical complications related to hypothermia Findings from this preliminary study may provide data for a future grant to launch a larger randomized controlled trial in the prehospitalin-hospital trauma setting to optimize the care of patients at risk of developing hypothermia
Current warming strategies increase the logistical difficulty of transferring patients which is frequent during the initial hours of trauma care or must be changed at frequent intervals Prehospital military and intraoperative studies have suggested chemical warming blankets as a pragmatic strategy to manage hypothermia A recent pilot study manuscript under review at our institution demonstrated the feasibility of using the Ready-Heat TechTrade LLC Orlando FL USA chemical heating blanket in the initial phases of hospital care in bleeding trauma patients requiring a mass hemorrhage protocol MHP These self-warming blankets provide warmth over 8 hours at up to 40 degrees Celsius carrying the advantage of portability with no continuous electric power requirement Furthermore the Ready-Heat blanket may be more effective than current strategies for rewarming patients at high risk of developing hypothermia STAYWARM-2 will be the first randomized controlled trial performed in-hospital to evaluate a self-warming blanket to address hypothermia in massively bleeding trauma patients within the initial hours of hospital arrival
This study will help to determine the efficacy and feasibility of using chemical heating blankets for hypothermia in the early hours of hospital care This has potential to reduce the overall workload of direct care clinicians freeing them for other patient care duties Additionally the intervention may achieve enhanced thermoregulation compared to current strategies improving patient care and comfort and avoiding the clinical complications related to hypothermia Findings from this preliminary study may provide data for a future grant to launch a larger randomized controlled trial in the prehospitalin-hospital trauma setting to optimize the care of patients at risk of developing hypothermia
Detailed Description:
Patient screening recruitment and enrolment Recruitment will occur in the trauma bay during weekdays between 0800-2000hrs by Staff Trauma Team Leaders with experience in QI initiatives and enrollment of severely bleeding trauma patients in clinical trials Due to the high acuity of the patient condition who usually needs multiple emergent interventions consent will be obtained retrospectively delayed consenting process In addition by seeking the patients consent for enrollment during a tenuous point in their care there is a potential of introducing bias or concerns about coercion into accepting any care related to the initial resuscitation
As soon as possible following the randomization and inclusion the patient if able to comprehend or substitute decision maker SDM will be approached about the study They will have their specific warming intervention explained and will have at that point the right to request that their data are withdrawn from the study
Study personnel will contact the MRP for permission to approach the patient or ask that they introduce the study to the patient With permission to enter the patients circle of care the research coordinator will then approach patients who were randomized and included in the study The research coordinator will introduce the trial confirm eligibility and conduct the informed consent discussion This discussion will include the rationale for the study the anticipated risks and benefits of participation and their rights as a study participant including withdrawal at any time Capable participants will be offered an opportunity to ask questions and consult with their family andor their physician before making a decision to continue in the study If the patient is deemed incapable of providing informed consent for the study study personnel will approach the SDM and go over the same process to obtain the consent Patients or SDM will be given an Informed Consent Form to be signed at this point
One signed copy of the informed consent will be placed in the participants medical record another copy given to the participant and the original kept in the study file with the research coordinator If the participant does not wish to participate the reason for declining will be documented
Patients will be randomized upon activation of the MHP according to a computer-generated allocation sequence using RedCap If the patient is randomized to receive the intervention the blood bank technologist will activate the two Ready-Heat blankets by opening the seal on the packaging The opened blankets will be attached outside of the first cooler of the MHP with red blood cells units sent to the trauma bay The cooler will be transported by a porter taken to the trauma bay and delivered to the trauma team As this is an open-label trial only the statistician will remain blinded during the final analysis Enrollment will occur 0800-2000hrs on weekdays with the aim of assessing feasibility of using the blanket when study coordinators are not always available to reinforce temperature monitoring proper blanket placement and compliance with keeping the blanket on the patient over the intervention period
Data will be collected by the research assistants and medical students as the patients are enrolled in the trial during weekdays 8 am to 8 pm The Trauma Team Video Review Program already implemented in the trauma bay captures imaging and sound for all trauma resuscitations The video review will permit granular data collection from admission to the trauma bay until the patient is transferred to the next phase of care REDCap will be used to register the collected variables
Research Ethics Board REB approval of the protocol and the informed consent form will be obtained A recruitment log of eligible and ineligible patients as well as reasons for non-consent will be kept We anticipate that this study will take 24 months to complete
Storage and Stability As per manufacturers Instructions for Use IFU document the Ready-Heat blanket may be stored in its air-tight protective packaging until ready for use Upon removing the outer packing the product will reach operating temperature within 15-20 minutes and will remain functional for up to 10 hours After use the blanket can be disposed of with regular waste as there are no harmful ingredients The Blood Bank will maintain a stock of the Ready-Heat blankets and stored at room temperature The study product will be dispensed to those randomized to the intervention arm along with the first MHP pack of blood products
Dispensing of Investigational Product The Ready-Heat blanket will be provided to randomized patients by the Blood Bank along with the first MHP pack of blood products An instruction sheet will be provided specifying how to apply the Ready-Heat blanket while avoiding direct skin contact Instructions will be provided to keep the interventional products until the 8 hours post blanket application is completed
Return and Destruction of Investigational Product Trauma Team members will be made aware of their responsibility to return any unused investigational products in the event the resuscitation is ended before applying the product ie patient death termination of resuscitation As per manufacturers Instructions for Use IFU document the Ready-Heat blanket may be disposed of with regular waste as there are no harmful ingredients
Study Visits and Assessments Study visits will be conducted by research assistants during weekdays to collect data
Study Visits
The following information will be collected during study visits either in person or remotely reviewing electronic health records and video recordings of patient resuscitations in the trauma bay During weekdays 8 am to 8 pm the research assistant will be following the patient across the different phaseslocations of care and will be collecting data at the same time Video recordings will be performed as per Trauma Team Video Review policy for all patients Video review will be used to assess time of blanket application in the Trauma Bay and reasons why the blanket was not applied or was removed Research assistants will access all documented data and video recordings on the next weekday Visits and specific data collection are detailed as follows
Visit 1
On admission to the trauma bay Demographics injury characteristics and surgical management
1 Date of injury
2 Time of injury
3 Sex
4 Age
5 Types of surgical procedures performed in the first 8 hours following hospital arrival
6 Date of arrival
7 Time of arrival
8 Time of randomization
9 Name of attending TTL and sub-TTL if applicable
10 Initial temperature recorded
11 Was the blanket placed on the patient YesNo
12 Time that the blanket was placed on the patient if registered
13 Reason why blanket was not applied
14 Blanket applied directly to the patients skin YesNo
15 Use of fluid warmers
16 Use of FAWB
Visit 2
Within the first eight hours of blanket application
1 Location of the patient
2 Is the blanket kept on the patient YesNo
3 If not what was the reason it was removed
4 Temperature recorded hourly YesNo
5 If yes the temperature recorded
6 Type of temperature measurement
7 Blanket applied directly to patients skin YesNo
8 Use of FAWB
9 Use of fluid warmers
At discretion of the clinician within the first eight hours of blanket application
10 Coagulation platelet count INR fibrinogen
11 Perfusion parameters pH base deficit serum lactate
12 Hemoglobin
13 Number of units of red blood cells plasma platelets and fibrinogen concentrate administered within the first 8 hours
Visit 3
At 24 hours post blanket application
1 Number of units of red blood cells plasma platelets and fibrinogen concentrate administered within the first 24 hours
2 Type of injury bluntpenetrating
3 Injury Severity Score ISS
4 Frequency of safety events with skin
Compliance Monitoring and Assessment Throughout the study duration compliance with application of the control or study intervention will be directly observed by research assistants on study visits and retrospective review of video recordings in the trauma bay and the health records The feasibility of adherence to temperature monitoring and blood and serum monitoring as per clinician discretion will be evaluated Any use of concurrent warming strategies ie fluid warmers FAWB etc will also be recorded
Protocol Deviations Planned or unplanned deviations may occur on the part of the participant the investigator or study research team In resolution to a deviation correctivepreventative actions are to be developed and implemented in a timely manner to avoid subsequent deviations Protocol deviations will be documented and reported as required and assessed where necessary during analysis If a control or study intervention is noted to not be in use or key data are missing from the health record a reason for noncompliance will be documented Based on findings from STAYWARM1 reasons for noncompliance are hypothesized to arise from patient condition and lack of familiarity with the study protocol Several educational initiatives will be developed prior to study commencement for trauma team members to avoid protocol deviations during the study period
ASSESSMENT OF SAFETY Definitions Adverse Event An Adverse Event AE is defined as any new event that may jeopardize the patient which the study investigator physician perceives may be directly related to the enrolment in the pilot study or to the assigned arm Adverse events are not study related if they are related primarily to the underlying disease All AEs are to be documented and assessed for relatedness If related to the study intervention and occurring from baseline up to 24 hours by the final visit the AE will be recorded on the eCRF and coded as per the most recent edition of the Common Terminology Criteria for Adverse Events CTCAE
Expected adverse events with Ready-Heat blankets Prolonged direct skin contact with the Ready-Heat blanket has been known to cause mild burns The manufacturer specifies the need for careful supervision when used with the elderly people with sensitive skin and those who cant feel heat or regulate heat13 Given that some of the enrolled patients may be sedated due to clinical condition the study products will be applied with the express direction to avoid direct skin contact The recommendation will be made to use a standard blanket as an intermediary between the skin and the study product
Unexpected Adverse Event An unexpected adverse event is defined as any adverse event that is not identified as expected or in nature severity or frequency in the current Health Canada Product Monograph
Serious Adverse Event SAE
A serious adverse event SAE in the study is defined as
1 any event that is fatal or immediately life threatening permanently disabling severely incapacitating or requires prolonged inpatient hospitalization or
2 any event that may jeopardize the patient and requires medical or surgical intervention to prevent one of the outcomes listed above AND
3 which the attending physician perceives may be directly related to enrolment in the study or to the assigned arm
SAEs will be considered to be study-related if the event follows a reasonable temporal sequence from the study intervention and could readily have been produced by the intervention Adverse events are not study related if they are related primarily to the underlying disease
Assessment of an Adverse Event Relationship CausalityRelatedness The causality assessment is the determination according to the investigators clinical judgment of the existence of a reasonable possibility that the investigational product IP caused or contributed to an adverse event
If the investigator or delegated sub-investigator is unsure about whether or not the study product caused or is related to the event then the event will be handled as related to the study product for reporting purposes of the trial If the causality assessment is unknown but not related to the study product this should be clearly documented in the source documents
Expectedness Events are classified as unforeseen or unexpected if the nature severity or frequency is not consistent with the risk information set out in Section 912 or the Product Monograph PM or label
Seriousness Events are classified as serious if associated with effects threatening the life or physiological functions of a participant Refer to the definition for Serious Adverse Events in section 915
Severity The term severe is often used to describe the intensity severity of a specific event eg mild moderate or severe myocardial infarction the event itself however may be of relatively minor medical significance such as severe headache This is not the same as serious which is based on participantevent outcome or action criteria usually associated with events that pose a threat to a participants life or functioning The terms serious and severe are not synonymous Seriousness not severity serves as a guide for defining regulatory reporting obligations
To assess the severity of an adverse event the investigators will use the following
the National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE
Adverse Event Recording Investigations into potential adverse events should be done during each contact with a participant Investigations may be done through specific questioning and as appropriate by examination Information on all adverse events should be recorded promptly in the source document and assessed by an investigator in a timely manner allowing sufficient time to meet required reporting timelines for SAEs and serious unexpected adverse drug reactions SUADRs if needed Adverse event CRFs should be completed using source documents by a delegated research team member in a timely mannerwithin 15 days of site awareness All clearly related signs symptoms and abnormal diagnostic procedures should be recorded in the source document though should be grouped under one diagnosis Each diagnosed adverse event should then be categorized in accordance with the revised NCI Common Terminology Criteria for Adverse Events CTCAE
The following are not considered AEs and therefore do not require recording
Pre-existing diseases or conditions identified and recorded at screeningbaseline unless at the discretion of the investigator the disease or condition worsens in severity or frequency
At the discretion of the investigator events considered likely manifestations of the underlying disease or that commonly occur in the study population independent of study drug exposure
Elective medical or surgical procedures
Procedures for Reporting a Serious Adverse Event and Unanticipated Events Investigator reporting Notifying the REB Serious adverse events and unanticipated events should be recorded and reported to the REB in accordance with local reporting requirements and timelines
Investigator reporting Notifying the Sponsor The investigator is responsible for reporting SAEs and SUADRs to the sponsor Sunnybrook Research Institute in accordance with applicable regulations and reporting requirements and timelines
Events that are assessed to be serious and unexpected and related or cannot be ruled out as related to the investigational product are considered SUADRs Reporting for SUADRs should include a description of the event in sufficient detail to allow for a complete medical assessment of the case and independent determination of possible causality The minimum information required includes at least one identifiable participant one identifiable reporter one serious reaction and one suspect product
Additionally for SAEs and SUADRS a Suspect Adverse Reaction Report - CIOMS I Form Appendix B must be completed by the investigator and forwarded to the Sponsor within 24 hours of site awareness Information on other possible causes of the event such as concomitant medications and illnesses should also be provided as soon as is made available
Sponsor Reporting of SUADRs Notifying Health Canada The regulatory sponsor is responsible for reporting SUADRs to regulatory authorities in accordance with local expedited reporting requirements and timelines In addition the Sponsor will complete the ADR Expedited Reporting Summary Form and submit this form in conjunction with the completed CIOMS Form to the appropriate Health Canada directorate
Sponsor Reporting of SUADRs Notifying Sites The regulatory sponsor is responsible for distributing expedited reports of SUADRs to each investigator for submission to local Ethics Committees within 15 days of sponsor awareness
Reporting and Entry Timelines
Study investigators will report SAEs to the sponsor within the following timelines
All deaths and immediately life-threatening events whether related or unrelated will be recorded and reported to the sponsor within 24 hours of site awareness
Serious adverse events other than death and immediately life-threatening events regardless of relationship will be reported to the sponsor within 72 hours of site awareness
Adverse event information will be entered into the CRF in a timely manner and no later than 15 days from the time the investigator becomes aware of the event
Serious adverse event information will be entered into the CRF in a timely mannerwithin 72 hours from the time the investigator becomes aware of the event
90 Early Termination and Reasons for Withdrawal
While it is not anticipated to cause discomfort patients may find that they are not able to continue with the study product due to the ongoing heat Patients are permitted to withdraw consent at any time if they desire and will not undergo further trial investigations if they do so Participants withdrawing from the study should be contacted by the study research team requesting a final visit and to follow up with any unresolved adverse events Once withdrawn from the study no further study procedures or evaluations should be performed or additional study data collected However every effort should be made to obtain permission to document the reason for withdrawal and to collect participant outcomes such as survival data up to the protocol-described end of participant follow up period where possible Any data collected prior to the withdrawal of consent may be retained and used by the sponsor If the patient withdraws from the study the research team will notify the patients most responsible physician
Data Collection and Follow-up for Withdrawn Participants Patients will be asked to continue with follow-up of body temperature and laboratory tests It is important to continue to follow these patients and capture outcomes that occur once they have discontinued study intervention to determine feasibility Through telephone calls and emails every effort will be made to obtain permission to document the reason participants withdrew consent and to continue collecting the body temperature and laboratory values previously mentioned Patients who have had at least one of the blankets applied will be included in the per-protocol analysis
ETHICAL ISSUES Ethical conduct and ethical issues Approval for patient accrual must be obtained from research ethics board REB at SHSC before patient recruitment can begin Any additional correspondence with REB must be maintained by the research coordinatorassistant
Informed Consent Due to the clinical condition of the patients during initial presentation screening and enrollment will be at the discretion of the Trauma Team Leader on an urgent basis When the patient is able to safely converse study personnel will approach the Most Responsible Physician MRP for permission to approach the patient With permission the research coordinator will then approach enrolled patients g to introduce the trial and conduct the informed consent discussion By being invited into the patients circle of care with the permission of the MRP study personnel will Introduce the rationale for the study the anticipated risks and benefits of participation and their rights as a study participant including withdrawal at any time Capable participants will be offered an opportunity to ask questions and consult with their family andor their physician before final decision If the patient is deemed medically incapable consent will be obtained from the substitute decision maker SDM One signed copy of the informed consent will be placed in the participants medical record another copy given to the participant and the original kept in the study file with the research coordinator If the participant does not wish to continue to participate the reason for declining will be documented and the patient will be considered a screening failure failure to provide informed consent
STUDY ADMINISTRATION This will be a single-site study conducted at Sunnybrook Health Sciences Centre The Research Coordinators supervised by the Principal Investigator will be responsible for trial coordination site training site start-upactivation document management supply management database development data management and statistical analysis Study data and patient surveys will be entered and maintained on a secure password protected database developed using REDCap wwwprojectredcaporg and will be accessible via the Internet for data entry purposes
Arrangements for day-to-day management of the trial The research coordinator will be responsible for this aspect of the study including system checks maintenance and data back-up Patient data will be collected as enrollment occurs and entered into the electronic case report forms Data queries will be generated monthly A bi-weekly status report will include an update on the recruitment and status of all randomized patients Monthly to bi-monthly audit and feedback meetings will be held Protocol violations will be audited and recorded on designated Protocol Violation Forms Clinical research coordinators will work with investigators on start-up activities REB applications study contract organizing study materials local in-services Thereafter research coordinators will screen consent and enroll patients complete case report forms and respond to data queries
Quality Assurance Study data will be maintained on a secure password protected database accessible from the world-wide-web Quality control will be ensured by oversight by the research coordinator at Sunnybrook Research Institute who will review the electronic data for all participants on a regular basis for completeness and consistency
Quality and completeness of data entry will be reviewed as soon as possible after data entry within five business days of data entry for the first five participants randomized and within 15 days of data entry thereafter Data queries generated by identification of incomplete or inconsistent data will be raised and should be resolved by the study coordinator or PI in a timely manner Corrections or changes in the data management system are tracked with the retention of the original data and the corrected data with the date of data entry and submitting personnel
As soon as possible following the randomization and inclusion the patient if able to comprehend or substitute decision maker SDM will be approached about the study They will have their specific warming intervention explained and will have at that point the right to request that their data are withdrawn from the study
Study personnel will contact the MRP for permission to approach the patient or ask that they introduce the study to the patient With permission to enter the patients circle of care the research coordinator will then approach patients who were randomized and included in the study The research coordinator will introduce the trial confirm eligibility and conduct the informed consent discussion This discussion will include the rationale for the study the anticipated risks and benefits of participation and their rights as a study participant including withdrawal at any time Capable participants will be offered an opportunity to ask questions and consult with their family andor their physician before making a decision to continue in the study If the patient is deemed incapable of providing informed consent for the study study personnel will approach the SDM and go over the same process to obtain the consent Patients or SDM will be given an Informed Consent Form to be signed at this point
One signed copy of the informed consent will be placed in the participants medical record another copy given to the participant and the original kept in the study file with the research coordinator If the participant does not wish to participate the reason for declining will be documented
Patients will be randomized upon activation of the MHP according to a computer-generated allocation sequence using RedCap If the patient is randomized to receive the intervention the blood bank technologist will activate the two Ready-Heat blankets by opening the seal on the packaging The opened blankets will be attached outside of the first cooler of the MHP with red blood cells units sent to the trauma bay The cooler will be transported by a porter taken to the trauma bay and delivered to the trauma team As this is an open-label trial only the statistician will remain blinded during the final analysis Enrollment will occur 0800-2000hrs on weekdays with the aim of assessing feasibility of using the blanket when study coordinators are not always available to reinforce temperature monitoring proper blanket placement and compliance with keeping the blanket on the patient over the intervention period
Data will be collected by the research assistants and medical students as the patients are enrolled in the trial during weekdays 8 am to 8 pm The Trauma Team Video Review Program already implemented in the trauma bay captures imaging and sound for all trauma resuscitations The video review will permit granular data collection from admission to the trauma bay until the patient is transferred to the next phase of care REDCap will be used to register the collected variables
Research Ethics Board REB approval of the protocol and the informed consent form will be obtained A recruitment log of eligible and ineligible patients as well as reasons for non-consent will be kept We anticipate that this study will take 24 months to complete
Storage and Stability As per manufacturers Instructions for Use IFU document the Ready-Heat blanket may be stored in its air-tight protective packaging until ready for use Upon removing the outer packing the product will reach operating temperature within 15-20 minutes and will remain functional for up to 10 hours After use the blanket can be disposed of with regular waste as there are no harmful ingredients The Blood Bank will maintain a stock of the Ready-Heat blankets and stored at room temperature The study product will be dispensed to those randomized to the intervention arm along with the first MHP pack of blood products
Dispensing of Investigational Product The Ready-Heat blanket will be provided to randomized patients by the Blood Bank along with the first MHP pack of blood products An instruction sheet will be provided specifying how to apply the Ready-Heat blanket while avoiding direct skin contact Instructions will be provided to keep the interventional products until the 8 hours post blanket application is completed
Return and Destruction of Investigational Product Trauma Team members will be made aware of their responsibility to return any unused investigational products in the event the resuscitation is ended before applying the product ie patient death termination of resuscitation As per manufacturers Instructions for Use IFU document the Ready-Heat blanket may be disposed of with regular waste as there are no harmful ingredients
Study Visits and Assessments Study visits will be conducted by research assistants during weekdays to collect data
Study Visits
The following information will be collected during study visits either in person or remotely reviewing electronic health records and video recordings of patient resuscitations in the trauma bay During weekdays 8 am to 8 pm the research assistant will be following the patient across the different phaseslocations of care and will be collecting data at the same time Video recordings will be performed as per Trauma Team Video Review policy for all patients Video review will be used to assess time of blanket application in the Trauma Bay and reasons why the blanket was not applied or was removed Research assistants will access all documented data and video recordings on the next weekday Visits and specific data collection are detailed as follows
Visit 1
On admission to the trauma bay Demographics injury characteristics and surgical management
1 Date of injury
2 Time of injury
3 Sex
4 Age
5 Types of surgical procedures performed in the first 8 hours following hospital arrival
6 Date of arrival
7 Time of arrival
8 Time of randomization
9 Name of attending TTL and sub-TTL if applicable
10 Initial temperature recorded
11 Was the blanket placed on the patient YesNo
12 Time that the blanket was placed on the patient if registered
13 Reason why blanket was not applied
14 Blanket applied directly to the patients skin YesNo
15 Use of fluid warmers
16 Use of FAWB
Visit 2
Within the first eight hours of blanket application
1 Location of the patient
2 Is the blanket kept on the patient YesNo
3 If not what was the reason it was removed
4 Temperature recorded hourly YesNo
5 If yes the temperature recorded
6 Type of temperature measurement
7 Blanket applied directly to patients skin YesNo
8 Use of FAWB
9 Use of fluid warmers
At discretion of the clinician within the first eight hours of blanket application
10 Coagulation platelet count INR fibrinogen
11 Perfusion parameters pH base deficit serum lactate
12 Hemoglobin
13 Number of units of red blood cells plasma platelets and fibrinogen concentrate administered within the first 8 hours
Visit 3
At 24 hours post blanket application
1 Number of units of red blood cells plasma platelets and fibrinogen concentrate administered within the first 24 hours
2 Type of injury bluntpenetrating
3 Injury Severity Score ISS
4 Frequency of safety events with skin
Compliance Monitoring and Assessment Throughout the study duration compliance with application of the control or study intervention will be directly observed by research assistants on study visits and retrospective review of video recordings in the trauma bay and the health records The feasibility of adherence to temperature monitoring and blood and serum monitoring as per clinician discretion will be evaluated Any use of concurrent warming strategies ie fluid warmers FAWB etc will also be recorded
Protocol Deviations Planned or unplanned deviations may occur on the part of the participant the investigator or study research team In resolution to a deviation correctivepreventative actions are to be developed and implemented in a timely manner to avoid subsequent deviations Protocol deviations will be documented and reported as required and assessed where necessary during analysis If a control or study intervention is noted to not be in use or key data are missing from the health record a reason for noncompliance will be documented Based on findings from STAYWARM1 reasons for noncompliance are hypothesized to arise from patient condition and lack of familiarity with the study protocol Several educational initiatives will be developed prior to study commencement for trauma team members to avoid protocol deviations during the study period
ASSESSMENT OF SAFETY Definitions Adverse Event An Adverse Event AE is defined as any new event that may jeopardize the patient which the study investigator physician perceives may be directly related to the enrolment in the pilot study or to the assigned arm Adverse events are not study related if they are related primarily to the underlying disease All AEs are to be documented and assessed for relatedness If related to the study intervention and occurring from baseline up to 24 hours by the final visit the AE will be recorded on the eCRF and coded as per the most recent edition of the Common Terminology Criteria for Adverse Events CTCAE
Expected adverse events with Ready-Heat blankets Prolonged direct skin contact with the Ready-Heat blanket has been known to cause mild burns The manufacturer specifies the need for careful supervision when used with the elderly people with sensitive skin and those who cant feel heat or regulate heat13 Given that some of the enrolled patients may be sedated due to clinical condition the study products will be applied with the express direction to avoid direct skin contact The recommendation will be made to use a standard blanket as an intermediary between the skin and the study product
Unexpected Adverse Event An unexpected adverse event is defined as any adverse event that is not identified as expected or in nature severity or frequency in the current Health Canada Product Monograph
Serious Adverse Event SAE
A serious adverse event SAE in the study is defined as
1 any event that is fatal or immediately life threatening permanently disabling severely incapacitating or requires prolonged inpatient hospitalization or
2 any event that may jeopardize the patient and requires medical or surgical intervention to prevent one of the outcomes listed above AND
3 which the attending physician perceives may be directly related to enrolment in the study or to the assigned arm
SAEs will be considered to be study-related if the event follows a reasonable temporal sequence from the study intervention and could readily have been produced by the intervention Adverse events are not study related if they are related primarily to the underlying disease
Assessment of an Adverse Event Relationship CausalityRelatedness The causality assessment is the determination according to the investigators clinical judgment of the existence of a reasonable possibility that the investigational product IP caused or contributed to an adverse event
If the investigator or delegated sub-investigator is unsure about whether or not the study product caused or is related to the event then the event will be handled as related to the study product for reporting purposes of the trial If the causality assessment is unknown but not related to the study product this should be clearly documented in the source documents
Expectedness Events are classified as unforeseen or unexpected if the nature severity or frequency is not consistent with the risk information set out in Section 912 or the Product Monograph PM or label
Seriousness Events are classified as serious if associated with effects threatening the life or physiological functions of a participant Refer to the definition for Serious Adverse Events in section 915
Severity The term severe is often used to describe the intensity severity of a specific event eg mild moderate or severe myocardial infarction the event itself however may be of relatively minor medical significance such as severe headache This is not the same as serious which is based on participantevent outcome or action criteria usually associated with events that pose a threat to a participants life or functioning The terms serious and severe are not synonymous Seriousness not severity serves as a guide for defining regulatory reporting obligations
To assess the severity of an adverse event the investigators will use the following
the National Cancer Institute NCI Common Terminology Criteria for Adverse Events CTCAE
Adverse Event Recording Investigations into potential adverse events should be done during each contact with a participant Investigations may be done through specific questioning and as appropriate by examination Information on all adverse events should be recorded promptly in the source document and assessed by an investigator in a timely manner allowing sufficient time to meet required reporting timelines for SAEs and serious unexpected adverse drug reactions SUADRs if needed Adverse event CRFs should be completed using source documents by a delegated research team member in a timely mannerwithin 15 days of site awareness All clearly related signs symptoms and abnormal diagnostic procedures should be recorded in the source document though should be grouped under one diagnosis Each diagnosed adverse event should then be categorized in accordance with the revised NCI Common Terminology Criteria for Adverse Events CTCAE
The following are not considered AEs and therefore do not require recording
Pre-existing diseases or conditions identified and recorded at screeningbaseline unless at the discretion of the investigator the disease or condition worsens in severity or frequency
At the discretion of the investigator events considered likely manifestations of the underlying disease or that commonly occur in the study population independent of study drug exposure
Elective medical or surgical procedures
Procedures for Reporting a Serious Adverse Event and Unanticipated Events Investigator reporting Notifying the REB Serious adverse events and unanticipated events should be recorded and reported to the REB in accordance with local reporting requirements and timelines
Investigator reporting Notifying the Sponsor The investigator is responsible for reporting SAEs and SUADRs to the sponsor Sunnybrook Research Institute in accordance with applicable regulations and reporting requirements and timelines
Events that are assessed to be serious and unexpected and related or cannot be ruled out as related to the investigational product are considered SUADRs Reporting for SUADRs should include a description of the event in sufficient detail to allow for a complete medical assessment of the case and independent determination of possible causality The minimum information required includes at least one identifiable participant one identifiable reporter one serious reaction and one suspect product
Additionally for SAEs and SUADRS a Suspect Adverse Reaction Report - CIOMS I Form Appendix B must be completed by the investigator and forwarded to the Sponsor within 24 hours of site awareness Information on other possible causes of the event such as concomitant medications and illnesses should also be provided as soon as is made available
Sponsor Reporting of SUADRs Notifying Health Canada The regulatory sponsor is responsible for reporting SUADRs to regulatory authorities in accordance with local expedited reporting requirements and timelines In addition the Sponsor will complete the ADR Expedited Reporting Summary Form and submit this form in conjunction with the completed CIOMS Form to the appropriate Health Canada directorate
Sponsor Reporting of SUADRs Notifying Sites The regulatory sponsor is responsible for distributing expedited reports of SUADRs to each investigator for submission to local Ethics Committees within 15 days of sponsor awareness
Reporting and Entry Timelines
Study investigators will report SAEs to the sponsor within the following timelines
All deaths and immediately life-threatening events whether related or unrelated will be recorded and reported to the sponsor within 24 hours of site awareness
Serious adverse events other than death and immediately life-threatening events regardless of relationship will be reported to the sponsor within 72 hours of site awareness
Adverse event information will be entered into the CRF in a timely manner and no later than 15 days from the time the investigator becomes aware of the event
Serious adverse event information will be entered into the CRF in a timely mannerwithin 72 hours from the time the investigator becomes aware of the event
90 Early Termination and Reasons for Withdrawal
While it is not anticipated to cause discomfort patients may find that they are not able to continue with the study product due to the ongoing heat Patients are permitted to withdraw consent at any time if they desire and will not undergo further trial investigations if they do so Participants withdrawing from the study should be contacted by the study research team requesting a final visit and to follow up with any unresolved adverse events Once withdrawn from the study no further study procedures or evaluations should be performed or additional study data collected However every effort should be made to obtain permission to document the reason for withdrawal and to collect participant outcomes such as survival data up to the protocol-described end of participant follow up period where possible Any data collected prior to the withdrawal of consent may be retained and used by the sponsor If the patient withdraws from the study the research team will notify the patients most responsible physician
Data Collection and Follow-up for Withdrawn Participants Patients will be asked to continue with follow-up of body temperature and laboratory tests It is important to continue to follow these patients and capture outcomes that occur once they have discontinued study intervention to determine feasibility Through telephone calls and emails every effort will be made to obtain permission to document the reason participants withdrew consent and to continue collecting the body temperature and laboratory values previously mentioned Patients who have had at least one of the blankets applied will be included in the per-protocol analysis
ETHICAL ISSUES Ethical conduct and ethical issues Approval for patient accrual must be obtained from research ethics board REB at SHSC before patient recruitment can begin Any additional correspondence with REB must be maintained by the research coordinatorassistant
Informed Consent Due to the clinical condition of the patients during initial presentation screening and enrollment will be at the discretion of the Trauma Team Leader on an urgent basis When the patient is able to safely converse study personnel will approach the Most Responsible Physician MRP for permission to approach the patient With permission the research coordinator will then approach enrolled patients g to introduce the trial and conduct the informed consent discussion By being invited into the patients circle of care with the permission of the MRP study personnel will Introduce the rationale for the study the anticipated risks and benefits of participation and their rights as a study participant including withdrawal at any time Capable participants will be offered an opportunity to ask questions and consult with their family andor their physician before final decision If the patient is deemed medically incapable consent will be obtained from the substitute decision maker SDM One signed copy of the informed consent will be placed in the participants medical record another copy given to the participant and the original kept in the study file with the research coordinator If the participant does not wish to continue to participate the reason for declining will be documented and the patient will be considered a screening failure failure to provide informed consent
STUDY ADMINISTRATION This will be a single-site study conducted at Sunnybrook Health Sciences Centre The Research Coordinators supervised by the Principal Investigator will be responsible for trial coordination site training site start-upactivation document management supply management database development data management and statistical analysis Study data and patient surveys will be entered and maintained on a secure password protected database developed using REDCap wwwprojectredcaporg and will be accessible via the Internet for data entry purposes
Arrangements for day-to-day management of the trial The research coordinator will be responsible for this aspect of the study including system checks maintenance and data back-up Patient data will be collected as enrollment occurs and entered into the electronic case report forms Data queries will be generated monthly A bi-weekly status report will include an update on the recruitment and status of all randomized patients Monthly to bi-monthly audit and feedback meetings will be held Protocol violations will be audited and recorded on designated Protocol Violation Forms Clinical research coordinators will work with investigators on start-up activities REB applications study contract organizing study materials local in-services Thereafter research coordinators will screen consent and enroll patients complete case report forms and respond to data queries
Quality Assurance Study data will be maintained on a secure password protected database accessible from the world-wide-web Quality control will be ensured by oversight by the research coordinator at Sunnybrook Research Institute who will review the electronic data for all participants on a regular basis for completeness and consistency
Quality and completeness of data entry will be reviewed as soon as possible after data entry within five business days of data entry for the first five participants randomized and within 15 days of data entry thereafter Data queries generated by identification of incomplete or inconsistent data will be raised and should be resolved by the study coordinator or PI in a timely manner Corrections or changes in the data management system are tracked with the retention of the original data and the corrected data with the date of data entry and submitting personnel
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None