Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00431379
Status:
WITHDRAWN
Last Update Posted:
2013-11-06
First Post:
2007-02-02
Brief Title:
Treatment of Acute Respiratory Distress Syndrome With Tenecteplase A Dose Escalation Pilot Study
Sponsor:
Medical Center of Central Georgia
Organization:
Medical Center of Central Georgia
Study Overview
Official Title:
Treatment of Acute Respiratory Distress Syndrome With Tenecteplase A Dose Escalation Pilot Study Phase I
Status:
WITHDRAWN
Status Verified Date:
2013-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
drug has expired no enrollments in study Company pulled funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The pathogenesis of ARDS appears to be from damage to the alveolar-capillary barrier which is composed of the microvascular endothelium and the alveolar epithelium This damage may occur from direct or indirect lung injury The mechanism of injury to the alveolar capillary barrier appears to be through neutrophil-mediated injury pro-inflammatory cytokines ventilator-induced lung injury with alveolar over distention and abnormalities of the coagulation system This results in blood clot formation in the microcirculation of the lung Thrombolytics can dissolve blood clots and result in increased blood flow to the organs This treatment may benefit ARDS patients thus the purpose of this study
Hardaway et alstudied the effects of thrombolytics on ARDS in pigs The experimental group showed improved oxygenation and survival as compared to controls There was no bleeding complications noted with this therapy Dr Hardaway followed this animal study with a phase I clinical trial involving 20 patients with ARDS The patients were treated with IV streptokinase or urokinase Nineteen of the 20 patients showed an increase in PA02 after thrombolytic therapy There were no significant bleeding complications in patients that were critically ill on ventilators
We propose an additional phase I pilot study to evaluate the effectiveness and safety of Tenecteplase for the treatment of ARDS Unlike the other fibrinolytics studied in this disease state Tenecteplase is more fibrin specific and has increased resistance to plasminogen activator inhibitor PAI-I at greater levels than other available fibrinolytics We have chosen an experimental dose escalation trial design of tenecteplase that has demonstrated initial safety trends in a Phase I acute ischemic stroke trial The initial dose is 01 mgkg IV and will increase to 02 mgkg 03 mgkg with a final cohort of patients receiving 04 mgkg Drug administration will be a single dose bolus in each cohort Advancement of dose will occur if safety is not in question in the previous cohort We hope this will provide an acceptable benefit risk ratio as the mortality of ARDS is approximately 30 - 60 All patients will be closely monitored for any change in clotting parameters and signs of bleeding Tenecteplase will be administered via a peripheral IV as described in the package insert
Hardaway et alstudied the effects of thrombolytics on ARDS in pigs The experimental group showed improved oxygenation and survival as compared to controls There was no bleeding complications noted with this therapy Dr Hardaway followed this animal study with a phase I clinical trial involving 20 patients with ARDS The patients were treated with IV streptokinase or urokinase Nineteen of the 20 patients showed an increase in PA02 after thrombolytic therapy There were no significant bleeding complications in patients that were critically ill on ventilators
We propose an additional phase I pilot study to evaluate the effectiveness and safety of Tenecteplase for the treatment of ARDS Unlike the other fibrinolytics studied in this disease state Tenecteplase is more fibrin specific and has increased resistance to plasminogen activator inhibitor PAI-I at greater levels than other available fibrinolytics We have chosen an experimental dose escalation trial design of tenecteplase that has demonstrated initial safety trends in a Phase I acute ischemic stroke trial The initial dose is 01 mgkg IV and will increase to 02 mgkg 03 mgkg with a final cohort of patients receiving 04 mgkg Drug administration will be a single dose bolus in each cohort Advancement of dose will occur if safety is not in question in the previous cohort We hope this will provide an acceptable benefit risk ratio as the mortality of ARDS is approximately 30 - 60 All patients will be closely monitored for any change in clotting parameters and signs of bleeding Tenecteplase will be administered via a peripheral IV as described in the package insert
Detailed Description:
1 Treatment of acute respiratory distress syndrome with tenecteplase a dose escalation pilot study phase I
2 The study sample size will be 20 patients The 20 patients will be divided into 4 groups with 5 patients in each group or cohort The first cohort will received 01mgkg of tenecteplase as a bolus via peripheral IV as described by the package insert and will be closely monitored for safety and efficacy If there are no adverse events associated with tenecteplase the second cohort of patients will be enrolled and will receive 02 mgkg of tenecteplase IV bolus If there are no safety issues we will proceed with the next cohort at 03 mgkg with a final cohort of patients receiving 04 mgkg of tenecteplase IV bolus Advancement of dose will occur if safety is not in question in the previous cohort
3 Tenecteplase will be given as a bolus via peripheral IV as described by package insert
4 Treatment will be initiated after informed consent is obtained and only 12 hrs after any subcutaneous Heparin has been stopped and 12 hrs after placement of a pulmonary artery catheter central line or arterial line Only patients meeting criteria for ARDS see inclusion criteria will be considered for the study
5 Pretreatment assessment We will obtain informed consent demographic data physical examination and medical history vital signs PT PTT INR ABG hemoglobin hematocrit liver enzymes cardiac enzymes creatinine fibrinogen fibrin split products platelets urine pregnancy test EKG chest x-ray cardiac profile from Swan-Ganz catheter and ventilator settings before treatment begins
6 Assessment during treatment Blood samples will be taken every 6 hours for 24 hours and analyzes for PT PTT INR fibrinogen fibrin split products platelets hemoglobin and hematocrit Arterial blood gas samples will be taken at hour 1 2 3 and every six hours until 24 hours post-injection Cardiac profile vital signs and ventilator settings will be monitored at hour 1 2 3 and every six hours until 24 hours post-infusion Adverse events will be monitored every hour for 24 hours
7 Follow-up assessment 72 hours post treatment physical exam vital signs weight adverse events cardiac profile ventilator settings PT PTT INR fibrinogen fibrin split products platelets ABG hemoglobin and hematocrit liver enzymes cardiac enzymes creatinine EKG and chest x-ray will be obtained Thirty days post treatment physical exam vital signs weight mortality adverse events will be followed
8 Patients will be monitored for signs of clinical bleeding
2 The study sample size will be 20 patients The 20 patients will be divided into 4 groups with 5 patients in each group or cohort The first cohort will received 01mgkg of tenecteplase as a bolus via peripheral IV as described by the package insert and will be closely monitored for safety and efficacy If there are no adverse events associated with tenecteplase the second cohort of patients will be enrolled and will receive 02 mgkg of tenecteplase IV bolus If there are no safety issues we will proceed with the next cohort at 03 mgkg with a final cohort of patients receiving 04 mgkg of tenecteplase IV bolus Advancement of dose will occur if safety is not in question in the previous cohort
3 Tenecteplase will be given as a bolus via peripheral IV as described by package insert
4 Treatment will be initiated after informed consent is obtained and only 12 hrs after any subcutaneous Heparin has been stopped and 12 hrs after placement of a pulmonary artery catheter central line or arterial line Only patients meeting criteria for ARDS see inclusion criteria will be considered for the study
5 Pretreatment assessment We will obtain informed consent demographic data physical examination and medical history vital signs PT PTT INR ABG hemoglobin hematocrit liver enzymes cardiac enzymes creatinine fibrinogen fibrin split products platelets urine pregnancy test EKG chest x-ray cardiac profile from Swan-Ganz catheter and ventilator settings before treatment begins
6 Assessment during treatment Blood samples will be taken every 6 hours for 24 hours and analyzes for PT PTT INR fibrinogen fibrin split products platelets hemoglobin and hematocrit Arterial blood gas samples will be taken at hour 1 2 3 and every six hours until 24 hours post-injection Cardiac profile vital signs and ventilator settings will be monitored at hour 1 2 3 and every six hours until 24 hours post-infusion Adverse events will be monitored every hour for 24 hours
7 Follow-up assessment 72 hours post treatment physical exam vital signs weight adverse events cardiac profile ventilator settings PT PTT INR fibrinogen fibrin split products platelets ABG hemoglobin and hematocrit liver enzymes cardiac enzymes creatinine EKG and chest x-ray will be obtained Thirty days post treatment physical exam vital signs weight mortality adverse events will be followed
8 Patients will be monitored for signs of clinical bleeding
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None