A Blind-adjudication Multi-center Phase II Randomized Clinical Trial of Continuous Low-dose Intravenous Heparin Therapy in Coiled Low-grade Aneurysmal Subarachnoid Hemorrhage Patients with Significant Hemorrhage Burden. - STUDY IS TEMPORARILY SUSPENDED WITH PLAN TO RESUME SOON. NO SAFETY CONCERNS
The primary objective of this study is to investigate the safety and clinical effect of a continuous low-dose intravenous unfractionated heparin (LDIVH) infusion for the prevention of aneurysmal subarachnoid hemorrhage (aSAH) induced neurocognitive dysfunction and other delayed neurological deficits. Additionally, increased blood and CSF levels of certain inflammatory biomarkers (IL-6, hsCRP, etc) have been correlated to aSAH patients with poor clinical outcomes. Unfractionated heparin (UFH) has known anti-inflammatory actions. As a result, a secondary objective of this study will be to evaluate whether LDIVH can reduce blood and CSF inflammatory biomarkers levels compared to controls and whether there is any association between inflammatory biomarker levels and cognitive outcomes in aSAH.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
88
Continuous intravenous infusion of a low-dose unfractionated heparin drip
Yale University
New Haven, Connecticut, United States
University of Florida
Gainesville, Florida, United States
Tallahassee Neurological Clinic
Tallahassee, Florida, United States
Rush University
Chicago, Illinois, United States
Montreal Cognitive Assessment (MoCA)
Primary Clinical Outcome Measure- mean score compared between groups
Time frame: 90-day follow-up visit
Rate of "Major Bleeding" or "Clinically Relevant Non-Major Bleeding"
As defined by the International Society of Thrombosis and Heamostasis (ISTH) Primary Safety Outcome Measure-
Time frame: Patients will be followed for the duration of the hospital stay; an expected average of 3 weeks
Rate of "Major Bleeding"
As defined by the International Society of Thrombosis and Haemostasis (ISTH)
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Rate of Type II Heparin Induced Thrombocytopenia (HIT)
Time frame: Enrollment through 90-day follow-up visit
Rate of Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE)
Time frame: Enrollment through 90-day follow-up visit
All Cause - Mortality Rate
Time frame: Enrollment through 90-day follow-up visit
Incidence of Any Fever (> 38.3 degrees C; > or = 101.0 degrees F)
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of multiple fevers (> 2 episodes)
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
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Indiana University
Indianapolis, Indiana, United States
University of Louisville
Louisville, Kentucky, United States
University of Michigan
Ann Arbor, Michigan, United States
Mount Sinai Ichan School of Medicine
New York, New York, United States
University of Texas Southwestern
Dallas, Texas, United States
Mean daily fever burden
Daily fever burden = Sum of hourly fever burden over 24 hours; Hourly fever burden = Any hourly temperature recording \> 37 degrees C - (minus) 37 degrees C; if temperature is less than or equal to 37 degrees C then the hourly fever burden would be zero.
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Glasgow Coma Score
Time frame: Enrollment, post-enrollment days #6, 10, discharge, and 90-day follow-up visit
National Institutes of Health Stroke Scale (NIHSS)
Time frame: Enrollment, post-enrollment days #6, 10, upon discharge from hospital stay an expected average of about 3 weeks after admission, 90-day follow-up visit
Montreal Cognitive Assessment (MoCA)
Mean between groups and rate of MoCA score of 20 or less between groups
Time frame: Enrollment, post-enrollment days #6, 10, 1 year follow-up
Center for Epidemiologic Studies Depression Scale (CES-D)
Time frame: 90-day follow-up visit and 1-year follow-up visit
Trail Making Test Parts A&B
Time frame: 90-day follow-up visit
Cerebral Vasospasm
Incidence of moderate and severe radiographic cerebral vasospasm (catheter angiogram, CTA, MRA) or incidence OR moderate and severe vasospasm by transcranial doppler (TCD) criteria
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of clinical cerebral vasospasm requiring rescue therapy
Rescue therapy = vasopressors or endovascular therapy for the purposes of reversing clinical vasospasm; it does not include Triple H (Hyperdynamic Therapy)
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Incidence of CT or MRI imaging demonstrating cerebral vasospasm related cerebral infarction
Time frame: Participants will be followed for the duration of the hospital stay, an expected average of 3 weeks
Ordinal Regression Analysis of the modified Rankin Scale score (mRS)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Relative frequency of "good outcome" as defined by dichotomized mRS score 0-2
Time frame: 90-day follow-up visit and 1 year follow-up visit
Barthel Index
Time frame: 90-day follow-up visit and 1 year follow-up visit
Return to work status
Time frame: 90-day follow-up and 1 year follow-up visit
Lawton instrumental activities of daily living (IADL)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Quality of Life in Brain Injury - Overall Scale (QOLIBRI-OS)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Checklist Individual Strength- Subscale Fatigue (CIS-F)
Time frame: 90-day follow-up visit and 1 year follow-up visit
Plasma biomarker level (hsCRP)
Time frame: Enrollment, post-enrollment days #2,4,6,10
Cerebrospinal Fluid (CSF) biomarker level (hsCRP)
Time frame: Enrollment, post-enrollment days #2,4,6,10
Rate of Serious Adverse Events (SAEs)
Secondary Safety Outcome Measure
Time frame: From enrollment through 90-Day follow-up visit