Platelet Function in Patients With Ischemic Stroke Treated With Anti-thrombotic or Thrombolytic

MEASUREMENT OF MARKERS OF PLATELET AGGREGATION AND INFLAMMATION IN ISCHEMIC STROKE SUBJECTS AFTER FIBRINOLYTIC/ANTI-THROMBOTIC USE. A PILOT STUDY.

Acute stroke afflicts nearly 700,000 patients in the US and is the number 3 cause of death. Only 2-9% of this large number is treated with t-PA if they arrive within 4.5 hours. An equally small percentage of patients with large vessel occlusion undergo thrombectomy.

The thrombectomy patients may or may not receive t-PA. Some of these patients rarely receive intravenous GPIIB/IIIa inhibitors. Many lines of evidence suggest that GP IIb/IIIa inhibitors, a class of FDA approved potent platelet inhibitors that have been used extensively along with heparin for acute coronary syndromes (heart attacks) and unstable angina (chest pain), may be safe enough to give in these circumstances.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Thrombolytic Agent

Detailed Description

In the past we used 30% lower dose of abciximab compared to the cardiac trials and the discontinued ABESTT stroke trial. There were no symptomatic intracranial hemorrhages or thromboyctopenia in our study. Based on the safety and efficacy results (Mandava et al, Translational Stroke Research 2010), we continued its use until manufacture of this agent was stopped.

There is another compound eptifibatide (Integrilin), that is also a GP IIb/IIIa which is in use in acute coronary syndromes. Eptifibatide has been used by cardiologists since 1998. Reduced doses have been studied along with intravenous rt-PA in stroke patients [Pancioli et al 2008 and 2013].

We are proposing even smaller dose compared to Pancioli et al 2008 and 2013. The reduced dose proposed here is less than 1/10th (<10%) cardiac dose. For an 80 kg patient the cardiac dose is 244 mg (14 mg bolus followed by an infusion of 230 mg over 24 hours). The reduced dose proposed here for stroke for an 80 kilogram patient is 10 mg bolus followed by an infusion of 10 mg over 24 hours. For patients weighing more than 80 kg the maximum bolus and infusion doses will remain 10 mg each. The cardiac dose does not specify a maximum weight.

If patients are eligible to receive alteplase as standard of care, patients will be offered alteplase.

Platelet aggregation has many poorly understood complex roles in ischemic stroke. We are planning on drawing three tubes of blood in addition before and after treatment. The tubes of blood will be collected at the bedside after consent and will be coordinated with the regularly scheduled blood draw that a patient undergoes at presentation to the emergency room. The three tubes of blood will be obtained and tests available in the laboratory will be performed. The three tests are Platelet Function Assay (PFA), Verify-Now (Aspirin) and Verify-Now(Plavix).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pitchaiah Mandava, MD PhD MSEE; Phone Number: 713 794 8906; Email: pmandava@bcm.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Michael E. DeBakey VA Medical Center
      • Contact: Pitchaiah Mandava, MD PhD MSEE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects are 18 years or older
2. Anterior Circulation stroke within the last six hours
3. Posterior Circulation stroke within the last 12 hours

Exclusion Criteria:

1. Initial CT of the head suggests stroke like symptoms are not due to an ischemic stroke but a result of hemorrhage or tumor
2. Platelet count below 100,000
3. PTT greater than 75 while on treatment with heparin
4. INR greater than 2.5 while on treatment with warfarin
5. ACT>250
6. Have clinical signs and symptoms of liver failure or elevations in AST, and ALT > 3 times the normal values.
7. Creatinine greater than 2
8. Treatment team considers the patient to be at increased risk of intra-cerebral hemorrhages or systemic bleeding
9. Pre-morbid modified Rankin score >2 suggesting a functionally dependent patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Measurement of Platelet function; Patients with ischemic stroke may be given alteplase or other thrombolytic. Additionally, patients may be given IV platelet inhibitors and subjected to thrombectomy. Platelet functions are measured after intervention.	Drug: Thrombolytic Agent; Subjects may receive one or more of the treatment options; Other Names: eptifibatide; thrombectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ninety day functional outcomes	Modified Rankin Score	Ninety days

Collaborators and Investigators

• Sponsor: Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): May 31, 2024

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 8, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Fibrinolytic Agents; Eptifibatide
• Other Study ID Numbers: H-31232

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes