Treating Patients With Aneurysmal SubArachnoid Hemorrhage (SAH) With Epoetin Alfa (EPO)

A Double Blinded, Placebo Controlled, Pilot Study to Evaluate the Safety of Treating Patients With Aneurysmal SubArachnoid Hemorrhage (SAH) With Epoetin Alfa

This is a prospective, randomized, double-blinded, placebo controlled pilot safety study that will enroll a total of twenty subjects. Subjects will be adults (30-75) who have sustained a SAH secondary to cerebral aneurysm rupture and who present with minimal neurological symptoms. All subjects will have a Hemoglobin less than or equal to 12 g/dL within 24 hours prior to study entry and undergo operative aneurismal clipping. Subjects will be randomized into two groups, ten subjects receiving the drug and ten subjects receiving the placebo. The subjects will receive three intravenous injections of study drug or placebo, once before undergoing operative aneurysmal clipping (study Day 1) and again for two additional days (study Day 2 and study Day 3).

There are 3 phases to this trial:

Screening Phase - patients will present with Subarachnoid hemorrhage (SAH) and prepped for surgery within 36 hours Treatment Phase - first pre-operative dose before surgery (Study Day 1), post-operative (Study Days 2 and 3) Follow-up Phase- Study Day 4 through discharge, 6-7 week follow-up Primary Objective: To determine the safety of administering intravenous doses of Procrit® once daily for three consecutive days to patients with aneurysmal SAH before and after vascular clipping by comparing the incidence of thrombotic events, hemoglobin and 6-7 week mortality between the Procrit® and placebo groups. Secondary Objectives: To determine if administration of Procrit® prior to aneurysm clipping reduces the incidence of vasospasm following a SAH event treated by vascular clipping. To determine if Procrit® administration prior to aneurysm clipping in patients with Aneurysmal SAH will improve neurological assessment scores in the post-SAH/post-clipping time period. To determine the feasibility of organizing a larger, randomized study to explore the neuroprotective effect of Procrit® in patients with Aneurysmal SubArachnoid Hemorrhage (SAH) when Procrit® is administered prior to surgical clipping of the aneurysm.

It is hypothesized that Procrit will provide a significant level of neuroprotection in the brain after an SAH event as a result of reduced cell death, as well as a reduced amount of vasospasm activity and delayed cerebral ischemia which can occur as a result of SAH. These factors may contribute to improved neurological functioning scores when compared to the placebo treated patients.

Study Overview

• Status: Terminated
• Conditions: Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Epoetin alfa; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age 30-75
• Patients undergoing vascular clipping post SAH
• Aneurysmal SAH as determined by history or clinical evaluation
• WFNS Score I and II
• Hb ≤ 12 g/dL within 36 hours prior to first dose of study drug
• Patients who receive Study drug and undergo surgical clipping of the aneurysm within 36 hours of the SAH event

Exclusion Criteria:

• Non-aneurysmal SAH
• WFNS Score III and higher
• Patients presenting with previous history of SAH
• Terminal, brain-dead, comfort care patients
• Patients not undergoing vascular clipping
• Hb > 12 g/dL
• Patients receiving blood transfusion prior to surgery
• Patients who currently receive Procrit or an EPO product
• Patients undergoing surgical clipping of the aneurysm greater than 36 hours after the SAH event
• Pregnancy or lactating
• Renal insufficiency (must present and maintain normal creatinine levels)
• Uncontrolled hypertension (systolic > 150 mmHg)
• Active or known seizure history within one year of SAH event
• Known history of thrombotic vascular events (PE, DVT, AMI, stroke)
• Allergy or sensitivity to mammalian derived products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Group A will receive Procrit® intravenous injections (40,000U) once daily for 3 days (Study Days 1, 2, and 3). The first dose of Procrit® will be given within 36 hours of the initial SAH event / symptoms and immediately before the vascular clipping procedure.	Drug: Epoetin alfa; Intravenous administration of epoetin alfa (40,000 IU) immediately before clipping surgery. Successive doses will be given 24 and 48 hours after the first dose.; Other Names: Procrit
Placebo Comparator: B; Group B will receive Saline intravenous injections once daily for 3 days (Study Days 1, 2, and 3).	Drug: Saline; 3ml of saline will be administered via an IV push immediately before clipping surgery. Successive doses will be given 24 and 48 hours after the first dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events After Administering Intravenous Doses of Procrit® Once Daily for Three Consecutive Days to Patients With Aneurysmal SAH Before and After Vascular Clipping	Number of adverse events	First 10 days following clipping and 6 week F/U

Secondary Outcome Measures

Outcome Measure	Time Frame
To Determine if Administration of Procrit® Prior to Aneurysm Clipping Reduces the Incidence of Vasospasm Following a SAH Event Treated by Vascular Clipping.	first 10 days following clipping and 6 week f/u
To Determine if Procrit® Administration Prior to Aneurysm Clipping in Patients With Aneurysmal SAH Will Improve Neurological Assessment Scores in the Post-SAH/Post-clipping Time Period	First 10 days following clipping and 6 week f/u
To Determine the Feasibility of Organizing a Larger, Randomized Study to Explore the Neuroprotective Effect of Procrit® in Patients With Aneurysmal SubArachnoid Hemorrhage (SAH) When Procrit® is Administered Prior to Surgical Clipping of the Aneurysm.	When all data is collected and analyzed

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: Ortho Biotech, Inc.
• Investigators: Principal Investigator: Enrico M Camporesi, MD, University of South Florida

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: February 7, 2008
• First Submitted That Met QC Criteria: February 28, 2008
• First Posted (Estimate): February 29, 2008

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 3, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: subarachnoid hemorrhage; Epoetin alfa; aneurysm
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 105838c; USF 6176-P67638