Ignite Creation Date:
2024-05-06 @ 8:11 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06288724
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-01
First Post:
2024-02-24
Brief Title:
MOdifiable facTors to Improve VentilAtion ThErapy in ICU
Sponsor:
Nat Intensive Care Surveillance - MORU
Organization:
Nat Intensive Care Surveillance - MORU
Study Overview
Official Title:
Potentially MOdifiable Factors To ImproVe Outcomes of Mechanically Ventilated Patients in ICUs in a Low-income Country Rationale and Protocol for a Registry-embedded Prospective Observational Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
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:
MOTIVATE-ICU
Brief Summary:
ABSTRACT Introduction Invasively ventilated patients in low and middle-income countries LMICs experience significantly higher mortality compared to those in High income countries HICs Direct application of HIC strategies to LMICs maybe ineffective due to context-specific challenges This study aims to leverage the Intensive Care Registry of Uganda ICRU to identify ICU structural and process-related modifiable factors that impact patient outcomes in a low income country
Methods The MOTIVATE-ICU is a prospective multicentre observational study in invasively ventilated patients It involves a registry-embedded component examining patient- and process-related factors and a cross-sectional survey on ICU organizational structures Inclusion criteria encompass patients aged 15 years undergoing IMV in Ugandan ICUs Primary outcomes are ICU mortality ICU length of stay LOS and duration of ventilation Secondary outcomes include ventilator-associated complications non-pulmonary organ support tTracheostomy outcomes will be explored in a pre-planned substudy Factors potentially associated with outcomes will be categorized into two groups non-modifiable factors and potentially modifiable Non-modifiable factors will include patient-related factors like age comorbidities and illness severity potentially modifiable factors include processes of care eg sedation levels and ICU organizational structure eg staffing patterns Multilevel multivariable logistic regression will be utilized to study associations with both patient and ICU level fixed effects considered
Ethics and Dissemination Given its observational nature this study seeks a waiver for patient individual informed consent Data anonymization ensures patient privacy Following the principles of the Declaration of Helsinki relevant ethical approvals will be acquired Study findings will be disseminated through conferences and peer-reviewed journals
Methods The MOTIVATE-ICU is a prospective multicentre observational study in invasively ventilated patients It involves a registry-embedded component examining patient- and process-related factors and a cross-sectional survey on ICU organizational structures Inclusion criteria encompass patients aged 15 years undergoing IMV in Ugandan ICUs Primary outcomes are ICU mortality ICU length of stay LOS and duration of ventilation Secondary outcomes include ventilator-associated complications non-pulmonary organ support tTracheostomy outcomes will be explored in a pre-planned substudy Factors potentially associated with outcomes will be categorized into two groups non-modifiable factors and potentially modifiable Non-modifiable factors will include patient-related factors like age comorbidities and illness severity potentially modifiable factors include processes of care eg sedation levels and ICU organizational structure eg staffing patterns Multilevel multivariable logistic regression will be utilized to study associations with both patient and ICU level fixed effects considered
Ethics and Dissemination Given its observational nature this study seeks a waiver for patient individual informed consent Data anonymization ensures patient privacy Following the principles of the Declaration of Helsinki relevant ethical approvals will be acquired Study findings will be disseminated through conferences and peer-reviewed journals
Detailed Description:
Introduction
In low and middle-income countries LMICs up to two-thirds of ICU admissions necessitate invasive mechanical ventilation IMV compared to half of ICU admissions globally1-3 Though IMV is a life saving organ support technique its also linked to complications like ventilator associated lung injury and requires complex processes of care4 Despite being younger ventilated patients in LMICs have 2-4 times higher mortality than high-income countries HICs5-8 Patients with acute respiratory distress syndrome ARDS in LMICs face an even greater risk 70 higher than in HICs9
While HICs have ample data on modifiable factors and improvement strategies that curtail ICU complications LMICs may face preventable complications associated with IMV110-13 Complications like ventilator-induced lung injury and related pneumonia lead not only to excess deaths but also longer ICU stays and escalating costs14 Unfortunately data on determinants of poor outcome among ventilated patients in LMICs remains scarce 1215-17 Directly applying HIC evidence based management strategies to LMICs isnt always effective as seen in several African trials 1819 LMICs grapple with challenges like understaffing limited training insufficient infrastructure and different patient characteristics and comorbidities all potentially compromising the quality of ICU care15162021
Recently the use of critical care registries for data collection including patient care indicators and outcomes has expanded in both HICs and LMICs22-24 This streamlines research and offers cost benefits Uganda has launched the Intensive Care Registry of Uganda ICRU for quality improvement and research infrastructure This registry-embedded study aims to identify modifiable factors impacting outcomes for mechanically ventilated patients in LMICs leveraging ICRUs data pipeline We hypothesize that specific patient-level and organizational factors can be identified that contribute to the ICU mortality of ventilated patients in Uganda
Methods and Analysis
Study design
The Potentially MOdifiable factors To ImproVe outcomes of mechanically Ventilated patients in ICUs in a Low-income Country MOTIVATE-ICU study is a prospective multicentre registry-embedded observational study with two main components The first will be a prospective observational multicenter registry-embedded study aimed at assessing patient-related and process-related factors The second component will be a cross-sectional survey to assess the organizational structure of the ICUs included This study protocol was registered at Clinicaltrialsgov registration number NCTXXXXXXX The results of the study will be reported according to the Strengthening the Reporting of Observational Studies in Epidemiology STROBE Statement25
Study setting
ICUs will be defined as geographically designated areaunit within a hospital that routinely provides invasive mechanical ventilation therapy with continuous vital sign monitoring electrocardiographic ECG monitoring heartpulse rate non-invasive blood pressure NIBP peripheral oxygen saturation SpO2 and designated nursing care for each bed in the unit ie at least three patients per week for at least 24 hours A descriptive study conducted in Uganda assessing the ICU capacity before the Corona virus induced disease 2019 COVID-19 revealed that at the time there were 14 ICUs with 12 being functional20 However post-COVID-19 anecdotal evidence shows nearly a doubling of the ICU capacity with nearly 25 functional ICUs to-date All ICUs currently functional in Uganda will be eligible to participate eTable 1
Participants
Patients aged 15 years admitted to study ICUs during the study period and receiving invasive mechanical ventilation will be eligible for recruitment Exclusion criteria include successful extubations within 24 hours of intubation admissions for end-of-life care andor ICU palliative support as well as patients transferred from ICUs not participating in the study 24 hours after initiation of MV
Outcomes
Primary outcomes The primary outcomes will be ICU mortality ICU length of stay LOS and duration of mechanical ventilation Outcome definitions are detailed in Table 1
Secondary outcomes These will include duration of non-pulmonary organ support ICU-free days ventilator-free days at day 28 ventilator-associated pneumonia VAP tracheobronchitis non-infectious pulmonary complication clinician suspicion or radiological diagnosis of pleural effusion atelectasis or pneumothorax readmission unplanned extubations Tracheostomy related outcomes will be explored as part of a preplanned substudy including tracheostomy timing decannulation rate decannulation failure and complications such as stoma infection major bleeding tube dislodgement and malfunction
Associated factors Table 2
Factors potentially associated with outcomes among mechanically ventilated patients will be analyzed as non-modifiable factors and potentially modifiable factors Non-modifiable factors include patient-related factors such as age illness severity at initiation of mechanical ventilation comorbidities medical vs surgical admission and indication for IMV Table 2 Potentially modifiable factors will subcategorized into care process-related factors such as Richmond Agitation Sedation Scale RASS targets initial ventilator settings on day 0 use of daily spontaneous awakening and spontaneous breathing trials use of stress ulcer and deep vein thrombosis DVT prophylaxis The second subcategory will be ICU organizational structure such ICU staffing staff-patient ratios empowerment of non-physician staff multidisciplinary team rounds and use of protocols and checklists Details on associated factors in supplementary material Table 2
Data collection
The following procedures will be performed to ensure the quality of the data collection Patient-level data will be entered directly via laptop or tablet through the cloud-based ICU registry platform PROTECT cloud-based platform of the ICRU currently in use Figure 1
Patient level variables of interest including age sex diagnostic categories functional capacity before hospital admission Clinical Frailty Score the Charlson Comorbidity Index the use of IMV on Day 1 modified Sequential Organ Function Assessment mSOFA and Tropical Intensive Care Score e-TropICS will be scored ICU level variables of interest included ICU type medical-surgical vs specialty presence of training programs in critical care ICU admission volumes in the preceding year staffing patterns organizational and process characteristics a full list of potential covariates is detailed in Table 2
We shall extract prospectively collected data from the ICRU platform which has both core data variables collected at admission and daily variables collected during the ICU stay
A complete list of variables is detailed in Supplementary materials The platform uses a common data model and provides real-time data on casemix management features and outcomes MOTIVATE-ICU study variables were incorporated into the PROTECT platform in order to design a registry embedded study Figure 1 The following site-level procedures will be followed
To ensure standardization of the study procedures each site shall have a site lead and dedicated data entrants responsible for data collection during use of the ICU registry platform Prior to the beginning of recruitment each site lead and data entrants will receive training
Each site will have a site lead responsible for weekly validation of patient episodes in terms of completion and data quality
Each site will have IT support as well as participate in monthly meetings as a means of dispelling doubts and solving potential challenges related to data entry
For each site data on hospital and ICU organizational and care process characteristics will be collected through an interviewer-administered questionnaire from the ICU director andor the in-charge nurse
Follow-up
Given the potential burden of data collection involved the patient recruitment period in each participating ICU will be a minimum of three months up to a maximum of 6 months with a 28-day maximum follow-up period for each patient recruited The follow up period for individual patients will end at ICU discharge
Procedures to ensure data quality
Sample size
We aim to include all consecutive patients admitted to participating ICUs in order to reduce potential selection bias and minimise temporal variation of care processes Based on aggregated data published and unpublished from LMICs including Ugandas ICU cohorts2101226-31 the lowest measured mortality among patients receiving invasive mechanical ventilation was approximately 40 A total of 250 events deaths would allow us to evaluate at least 25 associated variables in multivariable models We will therefore enroll at least 625 patients receiving invasive mechanical ventilation that fulfill the eligibility criteria
Handling of missing data
During the study period all data pertinent to the study objectives will be mandated for all study ICUs The study platform will flag missing data to the data collector in case of incompleteness Each site lead will ensure validation of patients entered and completeness of the data weekly to ensure no missing data This is being a prospective registry-embedded study we expect a low percentage of missing data pertinent to the primary objectives of the study
Statistical analysis
We will describe ICU and patient characteristics using standard descriptive statistics and reported continuous variables as mean standard deviation or median 25-75 interquartile range IQR as appropriate We will test the univariate association between eligible variables and outcomes using analysis of variance Kruskal-Wallis Student t test Mann-Whitney test chi-square test and Fisher exact test as appropriate
Using multilevel multivariable logistic regression models we shall investigate the association between organizational factors and the primary outcome adjusting for patients characteristics A two-level model will be fit with patient-level fixed effects at the first level and ICU-level fixed effects at the second level as well as an ICU-specific random effect We will pre-specify several models to represent the patients and the unit organization dimensions We shall then insert variables into the models if they are associated with outcome with a P value of 020 on univariate analysis We shall not consider variables used for e-TropICS score computation We shall apply several variables into the final model regardless of their statistical significance due to their clinical significance including the presence of 247 intensivist regular multidisciplinary rounds and nursebed ratios in the final model In addition we shall perform subgroup analyses stratifying patients according to the type of admission medical vs surgical and the e-TropICS tertiles We shall use the Akaike information criterion the likelihood ratios and the model residuals to choose among the alternative models Two-tailed P-values 005 were considered statistically significant All statistical analyses will be conducted in R httpwwwr-projectorg and SPSS 21 IBM Corp Armonk NY A detailed statistical analysis plan will be made available online before completion of the study and locking of the database
Ethics and dissemination
Ethical approval and consent to participate This study will be conducted according to the principles of the Declaration of Helsinki revision Fortaleza Brazil October 2013 Approval to carry out this study will be sought from the relevant ethical review and scientific review committees and from hospital administrations
We shall obtain deferred consent within 72 hours of recruitment into the study from the legal representative since most ICU admissions are emergency admissions and informed consent during the initial 48 hours of admission may not be possible In addition without exception patients admitted to ICU for ventilator support are unable to give informed consent Persons who may take the role of legal representative in accordance with the Medical Treatment Agreement Act WGBO are a predefined representative husband or wife registered partner or other life partner a parent or child brother or sister and incidentally a curator appointed by a judge For patients with no legal representative and are unable to give informed consent during in-hospital stay we shall obtain a waiver of consent The experience of ICU patients enrolled under deferred consent is mainly positive as shown in the NICE-SUGAR trial in which participants were included using deferred consent32 A majority of the patients were happy with the decision made by the representative 93 and would have granted consent if asked 9633
Oral consent from each of the ICU directors andor in-charge nurse will be sought to conduct the interviewer-administered survey
Dissemination
The study results will be submitted for publication regardless of the results after completion and analysis We shall make the study findings widely available including dissemination through conferences and peer-reviewed journals
Data sharing
The authors encourage interested parties to contact the corresponding author with data sharing requests including for access to additional unpublished data ICRU is part of a larger network which has appointed a Data Access Committee DAC Curated data may be shared with third parties for research purposes following written approval from the DAC
Discussion and study status
The MOTIVATE-ICU registry-embedded study aims to identify potentially modifiable factors associated with outcomes among invasively ventilated patients in a low income country
According to the Donabedian model improving the quality of healthcare and improving outcomes of interest rests on three components the structure care processes and outcomes34 Various studies from HICs on ICU organization structure care-bundles and protocols have shown significant impact in reduction of mortality duration of ventilation and ICU length of stay albeit with some inconsistencies in some aspects61135-37 Based on what we currently know from the ORCHESTRA study done in Brazil an upper middle income country UMIC organizational factors including protocol implementation are the key targets to improve ICU outcomes and efficiency3839 There has been considerable data describing the physical structural set-up and staffing of ICUs in LMICs20264041 but limited data is available on organizational features and care-processes and their impact on outcomes in lower income settings like Uganda
Direct implementation of evidence-based care processes from higher income settings may not necessarily yield similar results when implemented in resource-poor settings For example two African studies that implemented fluid therapy as per protocols used in HICs revealed more harm than benefit in both critically ill adults and paediatric populations1819 For other processes implementation in LMICs has improved consistently but outcomes remain lagging when compared to HICs probably affected by a multitude of factors For instance use of protective mechanical ventilation in patients without ARDS was shown to be comparable between MICs and HICS during first days of ventilation but with a large difference in ICU mortality14 The same was seen for ventilation in ARDS patients albeit with a small difference in protective ventilation implementation16
One of the key potential interventions likely to show impact in low-resource settings compared to HICs is tracheostomy placement and timing Tracheostomy timing while improving ICU length of stay and duration of mechanical ventilation has not had an impact on mortality in HICs42-44 but may have a significant impact in a setting with limited resources A preplanned substudy of MOTIVATE-ICU will explore timing complications and outcomes in patients undergoing tracheostomy in a low income country like Uganda complementing data from LMICs from other African countries4546
The strengths of the current study are its prospective design registry-embedded nature and multicenter inclusion There are several potential limitations of this study For example while efforts are made to ensure data quality and reduce missing data the reliance on electronic data collection and the prospective nature of the study may still encounter challenges with data completeness and accuracy across multiple centers The studys findings especially those related to organizational structure and process-related factors may be specific to the context of low-income countries and thus may not be generalizable to settings with different healthcare systems resources and ICU capabilities The cross-sectional survey assessing the organizational structure of ICUs rely on self-reported data which can introduce biases and inaccuracies
Acknowledgements
We thank all the site leads and data entrants of each site at each of the participating hospitals as well as Critical Care Asia Africa network for the support and involvement in the success of this study
Funding
The study will be supported by the Wellcome award Collaboration for Research Implementation and Training in Critical Care in Asia and Africa Grant number 224048Z21Z
In low and middle-income countries LMICs up to two-thirds of ICU admissions necessitate invasive mechanical ventilation IMV compared to half of ICU admissions globally1-3 Though IMV is a life saving organ support technique its also linked to complications like ventilator associated lung injury and requires complex processes of care4 Despite being younger ventilated patients in LMICs have 2-4 times higher mortality than high-income countries HICs5-8 Patients with acute respiratory distress syndrome ARDS in LMICs face an even greater risk 70 higher than in HICs9
While HICs have ample data on modifiable factors and improvement strategies that curtail ICU complications LMICs may face preventable complications associated with IMV110-13 Complications like ventilator-induced lung injury and related pneumonia lead not only to excess deaths but also longer ICU stays and escalating costs14 Unfortunately data on determinants of poor outcome among ventilated patients in LMICs remains scarce 1215-17 Directly applying HIC evidence based management strategies to LMICs isnt always effective as seen in several African trials 1819 LMICs grapple with challenges like understaffing limited training insufficient infrastructure and different patient characteristics and comorbidities all potentially compromising the quality of ICU care15162021
Recently the use of critical care registries for data collection including patient care indicators and outcomes has expanded in both HICs and LMICs22-24 This streamlines research and offers cost benefits Uganda has launched the Intensive Care Registry of Uganda ICRU for quality improvement and research infrastructure This registry-embedded study aims to identify modifiable factors impacting outcomes for mechanically ventilated patients in LMICs leveraging ICRUs data pipeline We hypothesize that specific patient-level and organizational factors can be identified that contribute to the ICU mortality of ventilated patients in Uganda
Methods and Analysis
Study design
The Potentially MOdifiable factors To ImproVe outcomes of mechanically Ventilated patients in ICUs in a Low-income Country MOTIVATE-ICU study is a prospective multicentre registry-embedded observational study with two main components The first will be a prospective observational multicenter registry-embedded study aimed at assessing patient-related and process-related factors The second component will be a cross-sectional survey to assess the organizational structure of the ICUs included This study protocol was registered at Clinicaltrialsgov registration number NCTXXXXXXX The results of the study will be reported according to the Strengthening the Reporting of Observational Studies in Epidemiology STROBE Statement25
Study setting
ICUs will be defined as geographically designated areaunit within a hospital that routinely provides invasive mechanical ventilation therapy with continuous vital sign monitoring electrocardiographic ECG monitoring heartpulse rate non-invasive blood pressure NIBP peripheral oxygen saturation SpO2 and designated nursing care for each bed in the unit ie at least three patients per week for at least 24 hours A descriptive study conducted in Uganda assessing the ICU capacity before the Corona virus induced disease 2019 COVID-19 revealed that at the time there were 14 ICUs with 12 being functional20 However post-COVID-19 anecdotal evidence shows nearly a doubling of the ICU capacity with nearly 25 functional ICUs to-date All ICUs currently functional in Uganda will be eligible to participate eTable 1
Participants
Patients aged 15 years admitted to study ICUs during the study period and receiving invasive mechanical ventilation will be eligible for recruitment Exclusion criteria include successful extubations within 24 hours of intubation admissions for end-of-life care andor ICU palliative support as well as patients transferred from ICUs not participating in the study 24 hours after initiation of MV
Outcomes
Primary outcomes The primary outcomes will be ICU mortality ICU length of stay LOS and duration of mechanical ventilation Outcome definitions are detailed in Table 1
Secondary outcomes These will include duration of non-pulmonary organ support ICU-free days ventilator-free days at day 28 ventilator-associated pneumonia VAP tracheobronchitis non-infectious pulmonary complication clinician suspicion or radiological diagnosis of pleural effusion atelectasis or pneumothorax readmission unplanned extubations Tracheostomy related outcomes will be explored as part of a preplanned substudy including tracheostomy timing decannulation rate decannulation failure and complications such as stoma infection major bleeding tube dislodgement and malfunction
Associated factors Table 2
Factors potentially associated with outcomes among mechanically ventilated patients will be analyzed as non-modifiable factors and potentially modifiable factors Non-modifiable factors include patient-related factors such as age illness severity at initiation of mechanical ventilation comorbidities medical vs surgical admission and indication for IMV Table 2 Potentially modifiable factors will subcategorized into care process-related factors such as Richmond Agitation Sedation Scale RASS targets initial ventilator settings on day 0 use of daily spontaneous awakening and spontaneous breathing trials use of stress ulcer and deep vein thrombosis DVT prophylaxis The second subcategory will be ICU organizational structure such ICU staffing staff-patient ratios empowerment of non-physician staff multidisciplinary team rounds and use of protocols and checklists Details on associated factors in supplementary material Table 2
Data collection
The following procedures will be performed to ensure the quality of the data collection Patient-level data will be entered directly via laptop or tablet through the cloud-based ICU registry platform PROTECT cloud-based platform of the ICRU currently in use Figure 1
Patient level variables of interest including age sex diagnostic categories functional capacity before hospital admission Clinical Frailty Score the Charlson Comorbidity Index the use of IMV on Day 1 modified Sequential Organ Function Assessment mSOFA and Tropical Intensive Care Score e-TropICS will be scored ICU level variables of interest included ICU type medical-surgical vs specialty presence of training programs in critical care ICU admission volumes in the preceding year staffing patterns organizational and process characteristics a full list of potential covariates is detailed in Table 2
We shall extract prospectively collected data from the ICRU platform which has both core data variables collected at admission and daily variables collected during the ICU stay
A complete list of variables is detailed in Supplementary materials The platform uses a common data model and provides real-time data on casemix management features and outcomes MOTIVATE-ICU study variables were incorporated into the PROTECT platform in order to design a registry embedded study Figure 1 The following site-level procedures will be followed
To ensure standardization of the study procedures each site shall have a site lead and dedicated data entrants responsible for data collection during use of the ICU registry platform Prior to the beginning of recruitment each site lead and data entrants will receive training
Each site will have a site lead responsible for weekly validation of patient episodes in terms of completion and data quality
Each site will have IT support as well as participate in monthly meetings as a means of dispelling doubts and solving potential challenges related to data entry
For each site data on hospital and ICU organizational and care process characteristics will be collected through an interviewer-administered questionnaire from the ICU director andor the in-charge nurse
Follow-up
Given the potential burden of data collection involved the patient recruitment period in each participating ICU will be a minimum of three months up to a maximum of 6 months with a 28-day maximum follow-up period for each patient recruited The follow up period for individual patients will end at ICU discharge
Procedures to ensure data quality
Sample size
We aim to include all consecutive patients admitted to participating ICUs in order to reduce potential selection bias and minimise temporal variation of care processes Based on aggregated data published and unpublished from LMICs including Ugandas ICU cohorts2101226-31 the lowest measured mortality among patients receiving invasive mechanical ventilation was approximately 40 A total of 250 events deaths would allow us to evaluate at least 25 associated variables in multivariable models We will therefore enroll at least 625 patients receiving invasive mechanical ventilation that fulfill the eligibility criteria
Handling of missing data
During the study period all data pertinent to the study objectives will be mandated for all study ICUs The study platform will flag missing data to the data collector in case of incompleteness Each site lead will ensure validation of patients entered and completeness of the data weekly to ensure no missing data This is being a prospective registry-embedded study we expect a low percentage of missing data pertinent to the primary objectives of the study
Statistical analysis
We will describe ICU and patient characteristics using standard descriptive statistics and reported continuous variables as mean standard deviation or median 25-75 interquartile range IQR as appropriate We will test the univariate association between eligible variables and outcomes using analysis of variance Kruskal-Wallis Student t test Mann-Whitney test chi-square test and Fisher exact test as appropriate
Using multilevel multivariable logistic regression models we shall investigate the association between organizational factors and the primary outcome adjusting for patients characteristics A two-level model will be fit with patient-level fixed effects at the first level and ICU-level fixed effects at the second level as well as an ICU-specific random effect We will pre-specify several models to represent the patients and the unit organization dimensions We shall then insert variables into the models if they are associated with outcome with a P value of 020 on univariate analysis We shall not consider variables used for e-TropICS score computation We shall apply several variables into the final model regardless of their statistical significance due to their clinical significance including the presence of 247 intensivist regular multidisciplinary rounds and nursebed ratios in the final model In addition we shall perform subgroup analyses stratifying patients according to the type of admission medical vs surgical and the e-TropICS tertiles We shall use the Akaike information criterion the likelihood ratios and the model residuals to choose among the alternative models Two-tailed P-values 005 were considered statistically significant All statistical analyses will be conducted in R httpwwwr-projectorg and SPSS 21 IBM Corp Armonk NY A detailed statistical analysis plan will be made available online before completion of the study and locking of the database
Ethics and dissemination
Ethical approval and consent to participate This study will be conducted according to the principles of the Declaration of Helsinki revision Fortaleza Brazil October 2013 Approval to carry out this study will be sought from the relevant ethical review and scientific review committees and from hospital administrations
We shall obtain deferred consent within 72 hours of recruitment into the study from the legal representative since most ICU admissions are emergency admissions and informed consent during the initial 48 hours of admission may not be possible In addition without exception patients admitted to ICU for ventilator support are unable to give informed consent Persons who may take the role of legal representative in accordance with the Medical Treatment Agreement Act WGBO are a predefined representative husband or wife registered partner or other life partner a parent or child brother or sister and incidentally a curator appointed by a judge For patients with no legal representative and are unable to give informed consent during in-hospital stay we shall obtain a waiver of consent The experience of ICU patients enrolled under deferred consent is mainly positive as shown in the NICE-SUGAR trial in which participants were included using deferred consent32 A majority of the patients were happy with the decision made by the representative 93 and would have granted consent if asked 9633
Oral consent from each of the ICU directors andor in-charge nurse will be sought to conduct the interviewer-administered survey
Dissemination
The study results will be submitted for publication regardless of the results after completion and analysis We shall make the study findings widely available including dissemination through conferences and peer-reviewed journals
Data sharing
The authors encourage interested parties to contact the corresponding author with data sharing requests including for access to additional unpublished data ICRU is part of a larger network which has appointed a Data Access Committee DAC Curated data may be shared with third parties for research purposes following written approval from the DAC
Discussion and study status
The MOTIVATE-ICU registry-embedded study aims to identify potentially modifiable factors associated with outcomes among invasively ventilated patients in a low income country
According to the Donabedian model improving the quality of healthcare and improving outcomes of interest rests on three components the structure care processes and outcomes34 Various studies from HICs on ICU organization structure care-bundles and protocols have shown significant impact in reduction of mortality duration of ventilation and ICU length of stay albeit with some inconsistencies in some aspects61135-37 Based on what we currently know from the ORCHESTRA study done in Brazil an upper middle income country UMIC organizational factors including protocol implementation are the key targets to improve ICU outcomes and efficiency3839 There has been considerable data describing the physical structural set-up and staffing of ICUs in LMICs20264041 but limited data is available on organizational features and care-processes and their impact on outcomes in lower income settings like Uganda
Direct implementation of evidence-based care processes from higher income settings may not necessarily yield similar results when implemented in resource-poor settings For example two African studies that implemented fluid therapy as per protocols used in HICs revealed more harm than benefit in both critically ill adults and paediatric populations1819 For other processes implementation in LMICs has improved consistently but outcomes remain lagging when compared to HICs probably affected by a multitude of factors For instance use of protective mechanical ventilation in patients without ARDS was shown to be comparable between MICs and HICS during first days of ventilation but with a large difference in ICU mortality14 The same was seen for ventilation in ARDS patients albeit with a small difference in protective ventilation implementation16
One of the key potential interventions likely to show impact in low-resource settings compared to HICs is tracheostomy placement and timing Tracheostomy timing while improving ICU length of stay and duration of mechanical ventilation has not had an impact on mortality in HICs42-44 but may have a significant impact in a setting with limited resources A preplanned substudy of MOTIVATE-ICU will explore timing complications and outcomes in patients undergoing tracheostomy in a low income country like Uganda complementing data from LMICs from other African countries4546
The strengths of the current study are its prospective design registry-embedded nature and multicenter inclusion There are several potential limitations of this study For example while efforts are made to ensure data quality and reduce missing data the reliance on electronic data collection and the prospective nature of the study may still encounter challenges with data completeness and accuracy across multiple centers The studys findings especially those related to organizational structure and process-related factors may be specific to the context of low-income countries and thus may not be generalizable to settings with different healthcare systems resources and ICU capabilities The cross-sectional survey assessing the organizational structure of ICUs rely on self-reported data which can introduce biases and inaccuracies
Acknowledgements
We thank all the site leads and data entrants of each site at each of the participating hospitals as well as Critical Care Asia Africa network for the support and involvement in the success of this study
Funding
The study will be supported by the Wellcome award Collaboration for Research Implementation and Training in Critical Care in Asia and Africa Grant number 224048Z21Z
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