Safety Study of Dantrolene in Subarachnoid Hemorrhage
Subarachnoid hemorrhage (SAH) is a devastating acute brain injury due to bleeding onto the brain surface from a ruptured aneurysm. Cerebral vasospasm (cVSP; critical narrowing of brain arteries) is a known complication after SAH and significantly increases disability and death after SAH. Vasospasm is difficult to treat and can lead to stroke. Animal studies have shown that the muscles in the artery wall play a role in cVSP.
Dantrolene has been FDA approved and extensively used in clinical practice as a muscle relaxant for more than 30 years. It has been shown to provide some benefit in animal studies of cVSP, as well as in a small number of humans. However, the first human studies have only been observational and over a short period of time.
This study will evaluate the safety and tolerability of intravenous dantrolene given every 6 hours over seven days to patients with or at risk for cVSP after SAH. The goal is to determine if future efficacy studies should be done to determine if treatment with Dantrolene may improve the outcome of patients with cVSP after SAH.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Dantrolene in the Prevention and Treatment of Cerebral Vasospasm in Subarachnoid Hemorrhage|
- Hyponatremia [ Time Frame: Seven days ] [ Designated as safety issue: Yes ]Number of subjects who developed hyponatremia (sNa ≤132mmol/L)
- Liver Toxicity [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]Number of subjects who developed liver toxicity as evidenced by Liver Function Test elevation greater than 5 times the upper limit of normal.
- In-hospital Mortality [ Time Frame: up to 90 days ] [ Designated as safety issue: No ]Number of subjects who expired during hospitalization.
|Study Start Date:||October 2009|
|Study Completion Date:||October 2013|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Dantrolene 1.25mg/kg IV every 6 hours x 7 days
Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days
Other Name: Dantrium
Placebo Comparator: Placebo
Equiosmolar volume (5% Mannitol)
equiosmolar volume (5% mannitol) every 6 hours x 7 days
Other Name: Free water/5% mannitol solution
Once eligibility criteria are met, patients will be randomized to either dantrolene-IV or placebo (equiosmolar, volume-equivalent sterile water with 5% mannitol as dantrolene-IV also contains 5% mannitol). Study subjects will be visited daily by a study nurse to determine side effects, tolerability, record hemodynamic measures and laboratory values. Patients will have daily serum Na, osmolality, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALK) measured. In addition, daily bedside transcranial doppler will be performed by a blinded examiner. Patients will undergo cerebral angiograms per clinical routine. Angiographic measurements of arterial narrowing will be performed by a blinded radiologist. Specific stop criteria are pre-defined.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01024972
|United States, Massachusetts|
|UMASS Medical School / UMass Memorial Medical Center|
|Worcester, Massachusetts, United States, 01655|
|Principal Investigator:||Susanne Muehlschlegel, MD||University of Massachusetts, Worcester|