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Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (CLEAR-FDR) (CLEAR-FDR)

Primary Purpose

Stroke, Brain Infarction

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Eptifibatide
Sponsored by
Arthur Pancioli
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring acute ischemic stroke, stroke, rt-PA, thrombolytic, t-PA, recombinant tissue plasminogen activator, Activase, eptifibatide, Integrilin, fibrinolytic agents, clot dissolving, blood clot

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have a serious measurable neurological deficit on the NIH Stroke Scale due to focal brain ischemia.
  • An NIH Stroke Scale score >5 at the time the rt-PA is begun.
  • Age: 18 through 85 years (i.e. candidates must have had their 18th birthday, but not had their 86th birthday).
  • Intravenous rt-PA therapy must be initiated within 3 hours of onset of stroke symptoms.

Exclusion Criteria:

  • History of stroke in the past 3 months.
  • Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
  • Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal.
  • Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mmHg or aggressive measures to lower blood pressure to below these limits are needed.
  • Presumed septic embolus.
  • Presumed pericarditis including pericarditis after acute myocardial infarction.
  • Recent (within 30 days) surgery or biopsy of parenchymal organ.
  • Recent (within 30 days) trauma, with internal injuries or ulcerative wounds.
  • Recent (within 90 days) severe head trauma or head trauma with loss of consciousness.
  • Any active or recent (within 30 days) serious systemic hemorrhage.
  • Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with International Normalized Ratio (INR) > 1.7.
  • Baseline lab values: positive urine pregnancy test, glucose < 50 or > 400 mg/dl, platelets <100,000 /mm3, Hct <25 %, or creatinine > 4 mg/dl.
  • Ongoing renal dialysis, regardless of creatinine.
  • Subjects who received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) as deep vein thrombosis (DVT) prophylaxis or in full dose within the previous 24 hours.
  • Subjects who received heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, or lepirudin) within 48 hours from screening must have had a normal partial prothrombin time (PTT).
  • Subjects who received Factor Xa inhibitors (such as fondaparinux) or direct thrombin inhibitors (such as dabigatran) within the last 4 days.
  • Arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days.
  • Seizure at onset of stroke.
  • Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.
  • Other serious, advanced, or terminal illness or any other condition that the investigator feels would pose a significant hazard to the patient if rt-PA or eptifibatide therapy were initiated.
  • Patients whose peripheral venous access is so poor that they are unable to have two standard peripheral intravenous lines started.
  • Current participation in another research drug treatment protocol. Patient cannot start another experimental agent until after 90 days.
  • Informed consent is not or cannot be obtained.
  • Any known history of amyloid angiopathy.
  • High density lesion consistent with hemorrhage of any degree.
  • Significant mass effect with midline shift.
  • Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment.

Sites / Locations

  • St. Elizabeth Healthcare System Edgewood
  • St. Elizabeth Healthcare Florence
  • St. Elizabeth Healthcare Ft. Thomas
  • The Christ Hospital
  • University of Cincinnati Medical Center
  • Good Samaritan Hospital
  • Jewish Hospital
  • Bethesda North Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eptifibatide

Arm Description

All subjects will receive the standard dose of IV rt-PA. All subjects will promptly receive an IV bolus of 135mcg/kg eptifibatide followed by an IV infusion of 0.75 mcg/kg/min eptifibatide for 2 hours.

Outcomes

Primary Outcome Measures

The Number of Patients Who Experience Symptomatic Intracerebral Hemorrhage (sICH).
Any ICH related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH. Judgment of significant neurological decline was made by the local clinical investigator

Secondary Outcome Measures

The Number of Patients Who Experience Any Intracerebral Hemorrhage (ICH).
Any ICH symptomatic (as defined above) or asymptomatic (that visualized on CT or MRI only)
The Number of Patients Who Develop Parenchymal Hemorrhage Types 1( PH-1) and 2 (PH-2).
Any parenchymal hemorrhage types PH-1 or PH-2 as visualized on CT

Full Information

First Posted
October 18, 2013
Last Updated
December 16, 2015
Sponsor
Arthur Pancioli
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT01977456
Brief Title
Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (CLEAR-FDR)
Acronym
CLEAR-FDR
Official Title
Phase 2 The Combined Approach to Lysis Utilizing Eptifibatide and Rt-PA in Acute Ischemic Stroke-Full Dose Regimen(CLEAR-FDR)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Arthur Pancioli
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary goal of this trial is to determine if individuals with acute ischemic stroke treated with a full dose of IV recombinant tissue plasminogen activator (rt-PA) plus IV eptifibatide started within 3 hours of symptom onset are more likely to have a better outcome than individuals treated with standard IV rt-PA alone.
Detailed Description
The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Full Dose Regimen (CLEAR-FDR Stroke Trial) is a Phase II trial and part of the Specialized Program on Translational Research in Acute Stroke (SPOTRIAS). The overall goals of SPOTRIAS are to enhance delivery of acute stroke patient care and train acute stroke translational researchers. Stroke most often occurs when blood flow to the brain stops because it is blocked by a blood clot. When a blood clot blocks the blood supply to the brain, parts of the brain may not get enough blood and oxygen to survive. As a result, permanent brain damage can occur, which can affect a person's ability to walk, talk, and function independently. In order to reduce the risk of permanent damage, it is important to restore blood flow to the brain as quickly as possible. rt-PA, used alone, is already approved by the Food and Drug Administration (FDA) as treatment for patients with a stroke caused by blockage of an artery in the brain and when given within 3 hours of the onset of stroke symptoms. Eptifibatide is also already FDA-approved as a treatment for blood clots causing heart attack. The investigational aspect of this study is the use of eptifibatide for a stroke victim in combination with rt-PA. The CLEAR Stroke Trial demonstrated that the combination of low dose rt-PA plus eptifibatide can be safely given to acute ischemic stroke patients within 3 hours of symptom onset. The CLEAR-ER Stroke Trial demonstrated that the combination of medium dose rt-PA plus eptifibatide can be safely given to acute ischemic stroke patients within 3 hours of symptom onset. The CLEAR-FDR Stroke Trial is designed to provide data concerning the risks when combining eptifibatide with full dose intravenous rt-PA in 30 acute ischemic stroke patients within 3 hours of symptom onset.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Brain Infarction
Keywords
acute ischemic stroke, stroke, rt-PA, thrombolytic, t-PA, recombinant tissue plasminogen activator, Activase, eptifibatide, Integrilin, fibrinolytic agents, clot dissolving, blood clot

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eptifibatide
Arm Type
Experimental
Arm Description
All subjects will receive the standard dose of IV rt-PA. All subjects will promptly receive an IV bolus of 135mcg/kg eptifibatide followed by an IV infusion of 0.75 mcg/kg/min eptifibatide for 2 hours.
Intervention Type
Drug
Intervention Name(s)
Eptifibatide
Other Intervention Name(s)
Integrilin
Intervention Description
IV Eptifibatide is an approved drug by the Food and Drug Administration as a treatment for blood clots causing heart attack and chest pain.Eptifibatide inhibits platelet aggregation by blocking activated platelets from binding fibrinogen.
Primary Outcome Measure Information:
Title
The Number of Patients Who Experience Symptomatic Intracerebral Hemorrhage (sICH).
Description
Any ICH related to a decline in neurologic status or the development of new neurologic symptoms which in the judgment of the clinical investigator was related to the ICH. Judgment of significant neurological decline was made by the local clinical investigator
Time Frame
within 36 hours after stroke onset
Secondary Outcome Measure Information:
Title
The Number of Patients Who Experience Any Intracerebral Hemorrhage (ICH).
Description
Any ICH symptomatic (as defined above) or asymptomatic (that visualized on CT or MRI only)
Time Frame
within 36 hours after stroke onset
Title
The Number of Patients Who Develop Parenchymal Hemorrhage Types 1( PH-1) and 2 (PH-2).
Description
Any parenchymal hemorrhage types PH-1 or PH-2 as visualized on CT
Time Frame
within 36 hours after stroke onset
Other Pre-specified Outcome Measures:
Title
The Number of Participants With Good Outcomes According to the Modified Rankin Score.
Description
Modified Rankin score (mRS) dichotomized to good outcome (mRS 0-1 or return to baseline), poor outcome (all others including death). Results reported are good outcome.
Time Frame
90 days from the date of stroke onset

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a serious measurable neurological deficit on the NIH Stroke Scale due to focal brain ischemia. An NIH Stroke Scale score >5 at the time the rt-PA is begun. Age: 18 through 85 years (i.e. candidates must have had their 18th birthday, but not had their 86th birthday). Intravenous rt-PA therapy must be initiated within 3 hours of onset of stroke symptoms. Exclusion Criteria: History of stroke in the past 3 months. Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal. Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mmHg or aggressive measures to lower blood pressure to below these limits are needed. Presumed septic embolus. Presumed pericarditis including pericarditis after acute myocardial infarction. Recent (within 30 days) surgery or biopsy of parenchymal organ. Recent (within 30 days) trauma, with internal injuries or ulcerative wounds. Recent (within 90 days) severe head trauma or head trauma with loss of consciousness. Any active or recent (within 30 days) serious systemic hemorrhage. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with International Normalized Ratio (INR) > 1.7. Baseline lab values: positive urine pregnancy test, glucose < 50 or > 400 mg/dl, platelets <100,000 /mm3, Hct <25 %, or creatinine > 4 mg/dl. Ongoing renal dialysis, regardless of creatinine. Subjects who received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) as deep vein thrombosis (DVT) prophylaxis or in full dose within the previous 24 hours. Subjects who received heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, or lepirudin) within 48 hours from screening must have had a normal partial prothrombin time (PTT). Subjects who received Factor Xa inhibitors (such as fondaparinux) or direct thrombin inhibitors (such as dabigatran) within the last 4 days. Arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days. Seizure at onset of stroke. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations. Other serious, advanced, or terminal illness or any other condition that the investigator feels would pose a significant hazard to the patient if rt-PA or eptifibatide therapy were initiated. Patients whose peripheral venous access is so poor that they are unable to have two standard peripheral intravenous lines started. Current participation in another research drug treatment protocol. Patient cannot start another experimental agent until after 90 days. Informed consent is not or cannot be obtained. Any known history of amyloid angiopathy. High density lesion consistent with hemorrhage of any degree. Significant mass effect with midline shift. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Opeolu Adeoye, MD
Organizational Affiliation
University of Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Elizabeth Healthcare System Edgewood
City
Edgewood
State/Province
Kentucky
ZIP/Postal Code
41017
Country
United States
Facility Name
St. Elizabeth Healthcare Florence
City
Florence
State/Province
Kentucky
ZIP/Postal Code
41042
Country
United States
Facility Name
St. Elizabeth Healthcare Ft. Thomas
City
Ft. Thomas
State/Province
Kentucky
ZIP/Postal Code
41075
Country
United States
Facility Name
The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Good Samaritan Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Facility Name
Jewish Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
Bethesda North Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26243231
Citation
Adeoye O, Sucharew H, Khoury J, Vagal A, Schmit PA, Ewing I, Levine SR, Demel S, Eckerle B, Katz B, Kleindorfer D, Stettler B, Woo D, Khatri P, Broderick JP, Pancioli AM. Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial. Stroke. 2015 Sep;46(9):2529-33. doi: 10.1161/STROKEAHA.115.010260. Epub 2015 Aug 4.
Results Reference
result

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Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (CLEAR-FDR)

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