Ignite Creation Date:
2025-12-25 @ 12:59 AM
Ignite Modification Date:
2025-12-27 @ 4:50 AM
Study NCT ID:
NCT00046293
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2002-09-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
ReoPro and Retavase to Treat Acute Stroke
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020521', 'term': 'Stroke'}], 'ancestors': [{'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077284', 'term': 'Abciximab'}], 'ancestors': [{'id': 'D007140', 'term': 'Immunoglobulin Fab Fragments'}, {'id': 'D007128', 'term': 'Immunoglobulin Fragments'}, {'id': 'D010446', 'term': 'Peptide Fragments'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'primaryPurpose': 'TREATMENT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 72}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2002-09-24'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2011-04-08', 'completionDateStruct': {'date': '2007-07-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-06-30', 'studyFirstSubmitDate': '2002-09-25', 'studyFirstSubmitQcDate': '2002-09-25', 'lastUpdatePostDateStruct': {'date': '2017-07-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2002-09-26', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2007-07-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical improvement at 24 hours after start of therapy.'}], 'secondaryOutcomes': [{'measure': 'Final infarct volume at day 30 CT adjusted for patient age and baseline NIHSS.'}]}, 'conditionsModule': {'keywords': ['Stroke', 'Abciximab', 'Retavase', 'MRI', 'Cerebral Blood Flow'], 'conditions': ['Cerebrovascular Accident']}, 'referencesModule': {'references': [{'pmid': '7477192', 'type': 'BACKGROUND', 'citation': 'National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.'}, {'pmid': '9788453', 'type': 'BACKGROUND', 'citation': 'Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 Oct 17;352(9136):1245-51. doi: 10.1016/s0140-6736(98)08020-9.'}, {'pmid': '7563451', 'type': 'BACKGROUND', 'citation': 'Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995 Oct 4;274(13):1017-25.'}]}, 'descriptionModule': {'briefSummary': 'This study will determine the dose of Retavase that can safely be combined with ReoPro in treating acute ischemic stroke (stroke resulting from a blood clot in the brain). ReoPro and Retavase are currently approved by the Food and Drug Administration to treat heart problems caused by blockage of heart arteries. The only therapy approved by the Food and Drug Administration to treat ischemic stroke is the clot buster drug rt-PA. This treatment is effective only if begun within 3 hours of onset of the stroke, however, and most patients do not get to the hospital early enough to benefit from it.\n\nPatients between 18 and 80 years of age who have had 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 medical history and physical examination, blood tests, rating of neurological deficits such as cognition deficits or problems walking that resulted from the stroke, and a computed tomography (CT) scan of the head. CT involves the use of specialized X-rays to obtain images of the brain. The patient lies on a table that is moved into a cylindrical machine (the scanner) for the imaging study, which usually takes about 5 to 10 minutes.\n\nAll participants will receive 0.25 mg/kg of ReoPro (maximum dose of 30 mg). The drug is infused into the vein over 12 hours. Some patients will also receive one of four doses of Retavase, which may boost the effectiveness of ReoPro in opening the blocked blood vessel. Retavase is given through a needle in the vein over 2 minutes. Patients will be monitored daily until discharge from the hospital, or until day 5, whichever is earlier. Assessments will include physical examinations, blood tests to examine factors involved in blood clotting, and CT scans to evaluate both the response to treatment and drug side effects. They will return for a follow-up examination and CT scan 30 days after treatment.\n\n...', 'detailedDescription': 'Objectives: This is the companion protocol to the ROSIE protocol. This clinical trial will determine an acceptable dose of reteplase in combination with a fixed dose of abciximab for ischemic stroke 3-24 hours from onset in patients screened with brain CT rather than MRI (as required by the ROSIE protocol). The importance of this study relative to ROSIE will be its relevance to the large proportion of acute stroke patients who cannot have a screening MRI, because of contraindications or unavailability of emergency MRI at their hospital.\n\nStudy 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, patients who cannot get acute MRI because of contraindication to or unavailability of MRI, acute ischemic stroke of moderate severity (NIH Stroke Scale less than or equal to 16 and ischemic changes on CT scan less than approximately one third of the volume of the middle cerebral artery territory), no evidence of hemorrhage on CT, and no other clinical, radiological or laboratory features associated with increased risk of hemorrhage with thrombolytic therapy.\n\nDesign: 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: 0.25 mg/kg bolus (to a maximum of 30 mg) followed by a 0.125 microgram/kg/minute infusion (to a maximum of 10.0 microgram/minute) for 12 hours. The five dosing groups for the reteplase dose are 0U, 2.5 U, 5.0 U, 7.5 U, and 10.0 U. A maximum of 72 patients will be treated using an adaptive statistical design. Non-investigation patient management will be standardized across all patients according to the NIH Stroke Center Clinical Care Pathway.\n\nOutcome Measures: The primary efficacy endpoint for response will be clinical improvement (complete recovery or improvement of 4 points or more on the NIH Stroke Scale) at 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 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "* INCLUSION CRITERIA\n\nPatients may be enrolled in the study only if they meet all of the following criteria:\n\nDiagnosis of acute ischemic stroke with onset between 3 and 24 hours prior to planned start of study drugs. Acute ischemic stroke is defined as a measurable neurological deficit of sudden onset, presumed secondary to focal cerebral ischemia, and not otherwise attributable to ICH or another disease process. Stroke onset will be defined as the time the patient was last known to be without the new clinical deficit. Patients whose deficits have worsened in the last 24 hours are not eligible if their first symptoms started more than 24 hours before. If the stroke started during sleep, stroke onset will be recorded as the time the patient was last known to be intact. A careful history is important to determine when the patient was last without the presenting deficits.\n\nDisabling neurological deficit attributable to the acute stroke at the start of study drugs.\n\nNIHSS less than or equal to16\n\nAge 18 - 80 years, inclusive.\n\nPatients not evaluable for the ROSIE protocol because of MRI contraindication or MRI unavailability or technically inadequate diffusion and perfusion MRI.\n\nEXCLUSION CRITERIA\n\nPatients will be excluded from the study for any of the following reasons:\n\nGeneral\n\nCurrent participation in another study with an investigational drug or device within, prior participation in the present study, or planned participation in another therapeutic trial, prior to the final assessment in this trial.\n\nTime interval since stroke onset of less than 24 hours is impossible to determine with high degree of confidence.\n\nSymptoms suggestive of subarachnoid hemorrhage, even if CT scan is negative for hemorrhage.\n\nEvidence of acute myocardial infarction defined as having at least two of the following three features: 1) Chest pain suggestive of cardiac ischemia 2) EKG findings of ST elevation of more greater than 0.2 mV in 2 contiguous leads, new onset left bundle branch block, ST segment depression, or T-wave inversion 3) Elevated troponin I\n\nWomen known to be pregnant, lactating or having a positive or indeterminate pregnancy test.\n\nPatients who would refuse blood transfusions if medically indicated\n\nStroke Related\n\nNeurological deficit that has led to stupor or coma (NIHSS level of consciousness score greater than or equal to 2).\n\nHigh clinical suspicion of septic embolus.\n\nMinor stroke with non-disabling deficit or rapidly improving neurological symptoms.\n\nBaseline NIHSS greater than 16.\n\nMRI/CT Related\n\nEvidence of acute or chronic ICH by head CT.\n\nCT evidence of non-vascular cause for the neurological symptoms.\n\nSigns of mass effect causing shift of midline structures.\n\nPatient excluded from the ROSIE protocol by MRI findings.\n\nAcute ischemic changes on CT larger than approximately one third of the territory of the middle cerebral artery territory by qualitative assessment.\n\nSafety Related\n\nPersistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greater than 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control.\n\nAnticipated need for major surgery within 72 hours after start of study drugs, e.g., carotid endarterectomy, hip fracture repair.\n\nAny intracranial surgery, serious head trauma (any head injury that required hospitalization), or stroke within the past 3 months.\n\nStroke within the past 3 months.\n\nHistory of ICH at any time in the past.\n\nMajor trauma at the time of stroke, e.g., hip fracture.\n\nBlood glucose greater than 200 mg/dl.\n\nPresence or history of intracranial neoplasm or arteriovenous malformation.\n\nIntracranial aneurysm, unless surgically treated greater than 3 months.\n\nMajor hemorrhage in past 21 days.\n\nMajor surgery, serious trauma, lumbar puncture, arterial puncture at a non-compressible site, or biopsy of a parenchymal organ in last 14 days. Major surgical procedures include but are not limited to the following: major thoracic or abdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy or other vascular surgery, and organ transplant. For non-listed procedures, the operating surgeon should be consulted to assess the risk.\n\nPresumed or documented history of vasculitis.\n\nKnown systemic bleeding disorder, e.g., von Willebrand's disease, hemophilia, others.\n\nPlatelet count less than 100,000 cells/mL.\n\nCongenital or acquired coagulopathy (e.g., secondary to anticoagulants) causing either of the following:\n\n1. Activated partial thromboplastin time (aPTT) prolongation greater than 2 seconds above the upper limit of normal for local laboratory, except if due to isolated factor XII deficiency. Protamine sulfate reversal of heparin effect does not alleviate this criterion.\n2. INR greater than or equal to 1.4. Patients receiving warfarin prior to entry are eligible provided INR is less than 1.4 and warfarin can be safely discontinued for at least 48 hours.\n\nPotentially Interfering with Outcome Assessment\n\nLife expectancy less than 3 months.\n\nOther serious illness, e.g., severe hepatic, cardiac, or renal failure; acute myocardial infarction; or a complex disease that may confound treatment assessment.\n\nSerum creatinine, AST or ALT greater than 3 times the upper limit of normal for the local laboratory.\n\nDrug Related\n\nTreatment of the qualifying stroke with any thrombolytic or GPIIbIIIa inhibitor outside of this protocol.\n\nAny administration of a thrombolytic drug in the prior 7 days.\n\nTreatment of the qualifying stroke with intravenous heparin unless aPTT prolongation is no greater than 2 seconds above the upper limit of normal for local laboratory prior to study drug initiation.\n\nTreatment of the qualifying stroke with a low molecular weight heparinoid.\n\nPrevious administration of abciximab, if known.\n\nKnown allergy to murine proteins.\n\nAnticoagulation caused by herbal therapy."}, 'identificationModule': {'nctId': 'NCT00046293', 'briefTitle': 'ReoPro and Retavase to Treat Acute Stroke', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'ReoPro Retavase Reperfusion of Stroke Safety Study-Imaging Evaluation With Computed Tomography (ROSIE-CT)', 'orgStudyIdInfo': {'id': '020301'}, 'secondaryIdInfos': [{'id': '02-N-0301'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'Reopro', 'type': 'DRUG'}, {'name': 'Retrovase', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Washington Hospital Center', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '20814', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'Suburban Hospital', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}, {'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institutes of Health Clinical Center, 9000 Rockville Pike', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Neurological Disorders and Stroke (NINDS)', 'class': 'NIH'}, 'responsibleParty': {'oldNameTitle': 'Steven J. Warach, M.D./National Institute of Neurological Disorders and Stroke', 'oldOrganization': 'National Institutes of Health'}}}}