Safety of Platelet Transfusion in Patients on Antiplatelet Therapy With Traumatic Head Injury (PUNCH)

The Safety and Efficacy of Platelet Transfusion in Patients Receiving Antiplatelet Therapy That Sustain Traumatic Intracranial Hemorrhage

The objective of this study is to determine if the administration of platelets will improve outcome in patients with ICH who are being treated with either aspirin, a thienopyridine (ticlodipine, clopidogrel, prasugrel) or a combination of both. The study has four specific aims:

1. To determine what affect platelet administration will have on bleeding in the brain.
2. To determine what affect platelet administration will have on brain function. Several assessments to test the functioning of the brain will be performed at enrollment and throughout the study. Comparing the results of these assessments between the experimental and control groups should allow us to determine if platelet administration improves outcomes in patients with bleeding in the brain exposed to antiplatelet therapy.
3. An important risk of reversing antiplatelet therapy is exposing the patient to the very complications this therapy was designed to prevent. Therefore, tracking complications will be a very important part of this study. The investigators will compare the rates of death, heart attack, stroke and clots in the veins between groups.
4. Some patients (10-40%) have limited responsiveness to antiplatelet therapy. While platelet responsiveness, as measured by a special platelet blood test, will not affect enrollment, the investigators feel it will be important to measure.

Study Overview

• Status: Terminated
• Conditions: Traumatic Head Injury; Intracranial Hemmorhage; Anti-platelet Therapy
• Intervention / Treatment: Other: Saline; Other: Platelets

Detailed Description

Intracranial hemorrhage (ICH), or bleeding in the brain, is the major cause of death in trauma patients. The initial volume and early growth of the hematoma are critical determinants of mortality and functional outcome. As our population ages, a significant and growing number of patients present with ICH while on antiplatelet therapy. Bleeding is a well known complication of this therapy. It is likely that patients with ICH who are exposed to antiplatelet therapy would have an increased risk of hemorrhage growth and poor outcome compared to patients that are not using antiplatelet therapy. There are no pharmacologic agents that can reverse the antithrombotic effect of aspirin or the thienopyridines. There is a paucity of published data, one small phase one trial and two retrospective studies that address the use of platelets as a means to reverse the effects of antiplatelet therapy in patients suffering ICH. In addition, transfusion of platelets may be associated with transfusion reactions, such as infection and fluid overload. Furthermore, these patients are then exposed to the very thromboembolic complications the antiplatelet therapy was designed to prevent.

Given the lack of data, which is primarily retrospective and likely underpowered, The investigators feel it's important to conduct a trial to more definitively study the efficacy of antiplatelet reversal in patients with life threatening ICH. Furthermore, it would be important to understand that, if there is a benefit to antiplatelet reversal in patients with ICH, that this benefit will outweigh the risks of antiplatelet reversal.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System, Christiana Hospital

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:

• 18 years or older
• Evidence of intracranial hemorrhage (bleeding in the brain) by CT scan related to traumatic injury
• Receiving antiplatelet therapy such as aspirin, thienopyridine (ticlopidine, clopidogrel, or prasugrel)
• Platelet count greater than or equal to 100,000

Exclusion Criteria:

• Glasgow Coma Scale (GCS) less than 6
• Hemorrhage requiring emergent surgery
• Lack of permission from treating physician and/or consultant
• Secondary ICH related to aneurysm or arteriovenous malformation
• Use of oral anticoagulants
• Decreased platelets (thrombocytopenia)
• Patients requiring massive transfusion protocol
• Life expectancy less than 3 months
• Confirmed acute heart attack
• Hepatitis and liver cirrhosis
• Kidney failure
• Participation in another treatment study within the preceding 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; 400 mL of Saline will be given intravenously over 2 hours once.	Other: Saline; 400 mL of Saline will be given intravenously over 2 hours once
Active Comparator: Platelets; 2 apheresis units of platelets (approximately 200 ml) will be given intravenously over 2 hours.	Other: Platelets; 2 apheresis units of platelets (approximately 200 ml) will be given intravenously over 2 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemorrhage growth	Bleeding in the brain will be measured by computerized tomography scan (CT Scan) 24 hours after study treatment is completed.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological Outcome	Assessments to determine brain function or neurological outcome will be performed at enrollment, time of study treatment, 1 and 24 hours post treatment, days 2, 3, and 10 (or time of discharge) and at 90 days post treatment.	Assessments to determine brain function or neurological outcome will be performed at enrollment, time of study treatment, 1 and 24 hours post treatment, days 2, 3, and 10 (or time of discharge) and at 90 days post treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboembolic complications	Complications such as heart attack, stroke, venous thromboembolic, and death which can be caused by reversing antiplatelet therapy will be monitored enrollment, time of study treatment, 1 and 24 hours post treatment, days 2, 3, and 10 (or time of discharge)and at 90 days post treatment.	Complications will be monitored enrollment, time of study treatment, 1 and 24 hours post treatment, days 2, 3, and 10 (or time of discharge)and at 90 days post treatment.
Platelet responsiveness	Platelet responsiveness will be measured by lab test at 1 and 24 hours post study treatment.	1 hour and 24 hours post study treatment

Collaborators and Investigators

• Sponsor: Christiana Care Health Services
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Mark Cipolle, Christiana Care Health Services

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: March 12, 2013
• First Posted (Estimate): March 13, 2013

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: April 14, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: platelets; intracranial hemorrhage; plavix; asprin; traumatic head injury; anti-platelet therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Trauma, Nervous System; Intracranial Hemorrhages; Craniocerebral Trauma
• Other Study ID Numbers: 601291; 31115 (Other Identifier: Christiana Care Health System)