Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00039832
Status:
COMPLETED
Last Update Posted:
2011-09-21
First Post:
2002-06-12
Brief Title:
ReoPro and Retavase to Restore Brain Blood Flow After Stroke
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
ReoPro Retavase Reperfusion of Stroke Safety Study - Imaging Evaluation
Status:
COMPLETED
Status Verified Date:
2011-09
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:
None
Brief Summary:
This study will evaluate the safety and effectiveness of two types of blood thinners abciximab ReoPro and reteplase Retavase for restoring normal brain blood flow after ischemic stroke stroke resulting from a blood clot in the brain
The only therapy approved by the Food and Drug Administration to treat ischemic stroke is the clot buster drug rt-PA This treatment however is effective only if begun within 3 hours of onset of the stroke and most patients do not get to the hospital early enough to benefit from it There is thus a pressing need to develop effective stroke treatments that can be initiated more than 3 hours after onset
Patients between 18 and 80 years of age who have experienced a mild or moderate acute stroke between 3 and 24 hours before starting study drugs may be eligible for this study Candidates will be screened with a physical examination blood tests and a magnetic resonance imaging MRI scan if an MRI was not done during the stroke evaluation
All participants will receive ReoPro Some will also receive Retavase which may boost the effectiveness of ReoPro Retavase is administered in a single dose through a needle in the vein over 2 minutes ReoPro is infused into the vein over 12 hours Patients will be monitored with physical examinations blood tests computed tomography CT scans and three or four MRI scans of the brain to evaluate both the response to treatment and side effects of the drugs An MRI scan will be done 24 hours 5 days and 30 days after starting the study medication and possibly during screening for this study
CT involves the use of specialized x-rays to obtain images of the brain The patient lies still in the scanner for a short time while the X-ray images are formed MRI uses a strong magnetic field and radio waves to demonstrate structural and chemical changes in tissue MRI is more sensitive than x-ray in evaluating acute stroke The patient lies on a table in a metal cylinder the scanner while the pictures are being taken During part of the MRI a medicine called gadolinium contrast is injected in a vein This medicine brightens the images creating better pictures of the blood flow
The only therapy approved by the Food and Drug Administration to treat ischemic stroke is the clot buster drug rt-PA This treatment however is effective only if begun within 3 hours of onset of the stroke and most patients do not get to the hospital early enough to benefit from it There is thus a pressing need to develop effective stroke treatments that can be initiated more than 3 hours after onset
Patients between 18 and 80 years of age who have experienced a mild or moderate acute stroke between 3 and 24 hours before starting study drugs may be eligible for this study Candidates will be screened with a physical examination blood tests and a magnetic resonance imaging MRI scan if an MRI was not done during the stroke evaluation
All participants will receive ReoPro Some will also receive Retavase which may boost the effectiveness of ReoPro Retavase is administered in a single dose through a needle in the vein over 2 minutes ReoPro is infused into the vein over 12 hours Patients will be monitored with physical examinations blood tests computed tomography CT scans and three or four MRI scans of the brain to evaluate both the response to treatment and side effects of the drugs An MRI scan will be done 24 hours 5 days and 30 days after starting the study medication and possibly during screening for this study
CT involves the use of specialized x-rays to obtain images of the brain The patient lies still in the scanner for a short time while the X-ray images are formed MRI uses a strong magnetic field and radio waves to demonstrate structural and chemical changes in tissue MRI is more sensitive than x-ray in evaluating acute stroke The patient lies on a table in a metal cylinder the scanner while the pictures are being taken During part of the MRI a medicine called gadolinium contrast is injected in a vein This medicine brightens the images creating better pictures of the blood flow
Detailed Description:
Objectives This is a clinical trial to determine an acceptable dose of reteplase in combination with a fixed dose of abciximab for ischemic stroke 3-24 hours from onset
Study Population Patients will be selected by criteria to minimize likelihood of toxicity and maximize likelihood of response These criteria include age 18-80 years old acute ischemic stroke of moderate severity NIH Stroke Scale less than or equal to 16 and lesion volume on diffusion MRI less than approximately one third of the volume of the middle cerebral artery territory positive MRI evidence of hypoperfusion corresponding to the acute stroke symptoms no MRI evidence of chronic micro-hemorrhages and no other clinical radiological or laboratory features associated with risk of hemorrhage with thrombolytic therapy
Design The study is open-label dose escalation safety and proof of principle study of the combination of intravenous abciximab and reteplase A fixed dose of abciximab will be used in all patients 025 mgkg bolus to a maximum of 30 mg followed by a 0125 microgramkgminute infusion to a maximum of 100 microgramminute for 12 hours The five dosing groups for the reteplase dose are 0 U 25 U 50 U 75 U and 100 U A maximum of 72 patients will be treated using an adaptive statistical design in which data on both the response and toxicity will be used to determine the dose for subsequent patients thereby minimizing exposure to either ineffective or toxic doses Non-investigational patient management will be standardized across all patients according to the NIH Stroke Center Clinical Care Pathway
Outcome Measures The primary efficacy endpoint for response will be reperfusion by MRI 24 hours after start of therapy The primary safety endpoint for determination of toxicity will be any one of the following symptomatic intracranial hemorrhage ICH major systemic hemorrhage or other serious adverse event related to study drug administration including death within 48 hours from start of therapy The maximum acceptable rate of toxicity will be 10 of patients treated at any dose level and the minimum acceptable rate of response will be 50 of patients treated at any dose level The outcomes will be monitored by a Data and Safety Monitoring Committee which will have the authority to stop or recommend modifications of the trial for safety concerns Other clinical outcome variables and imaging variables will be recorded and analyzed in secondary and exploratory analyses If an acceptable dose is identified then that will be investigated in a subsequent randomized placebo-controlled trial
Study Population Patients will be selected by criteria to minimize likelihood of toxicity and maximize likelihood of response These criteria include age 18-80 years old acute ischemic stroke of moderate severity NIH Stroke Scale less than or equal to 16 and lesion volume on diffusion MRI less than approximately one third of the volume of the middle cerebral artery territory positive MRI evidence of hypoperfusion corresponding to the acute stroke symptoms no MRI evidence of chronic micro-hemorrhages and no other clinical radiological or laboratory features associated with risk of hemorrhage with thrombolytic therapy
Design The study is open-label dose escalation safety and proof of principle study of the combination of intravenous abciximab and reteplase A fixed dose of abciximab will be used in all patients 025 mgkg bolus to a maximum of 30 mg followed by a 0125 microgramkgminute infusion to a maximum of 100 microgramminute for 12 hours The five dosing groups for the reteplase dose are 0 U 25 U 50 U 75 U and 100 U A maximum of 72 patients will be treated using an adaptive statistical design in which data on both the response and toxicity will be used to determine the dose for subsequent patients thereby minimizing exposure to either ineffective or toxic doses Non-investigational patient management will be standardized across all patients according to the NIH Stroke Center Clinical Care Pathway
Outcome Measures The primary efficacy endpoint for response will be reperfusion by MRI 24 hours after start of therapy The primary safety endpoint for determination of toxicity will be any one of the following symptomatic intracranial hemorrhage ICH major systemic hemorrhage or other serious adverse event related to study drug administration including death within 48 hours from start of therapy The maximum acceptable rate of toxicity will be 10 of patients treated at any dose level and the minimum acceptable rate of response will be 50 of patients treated at any dose level The outcomes will be monitored by a Data and Safety Monitoring Committee which will have the authority to stop or recommend modifications of the trial for safety concerns Other clinical outcome variables and imaging variables will be recorded and analyzed in secondary and exploratory analyses If an acceptable dose is identified then that will be investigated in a subsequent randomized placebo-controlled trial
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-N-0154 | None | None | None |