Subarachnoid Hemorrhage
Conditions
Keywords
Epoetin alfa, aneurysm, subarachnoid hemorrhage
Brief summary
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.
Interventions
DRUGEpoetin 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.
DRUGSaline
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.
Sponsors
Ortho Biotech, Inc.
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | First 10 days following clipping and 6 week F/U | Number of adverse events |
Secondary
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Procrit 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. | 2 |
| Saline Group B will receive Saline intravenous injections once daily for 3 days (Study Days 1, 2, and 3). | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Procrit | Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 1 / 1 |
Outcome results
Primary
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
Time frame: First 10 days following clipping and 6 week F/U
Population: Pilot Study- per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Procrit | 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 | 1 adverse events |
| Saline | 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 | 2 adverse events |
Secondary
To Determine if Administration of Procrit® Prior to Aneurysm Clipping Reduces the Incidence of Vasospasm Following a SAH Event Treated by Vascular Clipping.
Time frame: first 10 days following clipping and 6 week f/u
Population: Study terminated prematurely. Outcome measures were not analyzed.
Secondary
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
Time frame: First 10 days following clipping and 6 week f/u
Population: Study was terminated prematurely and outcome measures were not analyzed.
Secondary
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.
Time frame: When all data is collected and analyzed
Population: Study was terminated prematurely and outcome measures were not analyzed.