- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01024972
Safety Study of Dantrolene in Subarachnoid Hemorrhage
Dantrolene in the Prevention and Treatment of Cerebral Vasospasm 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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Worcester, Massachusetts, United States, 01655
- UMASS Medical School / UMass Memorial Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Documented aneurysmal SAH by computed tomography angiography (CTA), magnetic resonance angiography (MRA) or angiography
- Secured aneurysm (coiled or clipped)
- Enrollment achievable within 14 days after SAH
Exclusion Criteria:
- Pregnancy
- Prior history of cirrhosis or hepatitis B/C, or any two of the following three liver enzymes elevated to greater than: ALT >120 Units/L, AST >120 Units/L, alkaline phosphatase >345 Units/L (three times upper limit of normal)
- Patients on verapamil
- Patients with brain edema and/or elevated intracranial pressure (>25mm Hg)
- Patients treated with hypertonic saline or mannitol prior to enrollment
- Patients with too severe SAH with low likelihood of survival (Hunt & Hess 5)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Dantrolene
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 Names:
|
PLACEBO_COMPARATOR: Placebo
Equiosmolar volume (5% Mannitol)
|
equiosmolar volume (5% mannitol) every 6 hours x 7 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hyponatremia
Time Frame: Seven days
|
Number of subjects who developed hyponatremia (sNa ≤132mmol/L)
|
Seven days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Liver Toxicity
Time Frame: 7 days
|
Number of subjects who developed liver toxicity as evidenced by Liver Function Test elevation greater than 5 times the upper limit of normal.
|
7 days
|
In-hospital Mortality
Time Frame: up to 90 days
|
Number of subjects who expired during hospitalization.
|
up to 90 days
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Susanne Muehlschlegel, MD, University of Massachusetts, Worcester
Publications and helpful links
General Publications
- Salomone S, Soydan G, Moskowitz MA, Sims JR. Inhibition of cerebral vasoconstriction by dantrolene and nimodipine. Neurocrit Care. 2009;10(1):93-102. doi: 10.1007/s12028-008-9153-0. Epub 2008 Oct 16.
- Muehlschlegel S, Rordorf G, Bodock M, Sims JR. Dantrolene mediates vasorelaxation in cerebral vasoconstriction: a case series. Neurocrit Care. 2009;10(1):116-21. doi: 10.1007/s12028-008-9132-5. Epub 2008 Aug 12.
- Muehlschlegel S, Sims JR. Dantrolene: mechanisms of neuroprotection and possible clinical applications in the neurointensive care unit. Neurocrit Care. 2009;10(1):103-15. doi: 10.1007/s12028-008-9133-4. Epub 2008 Aug 12.
- Muehlschlegel S, Rordorf G, Sims J. Effects of a single dose of dantrolene in patients with cerebral vasospasm after subarachnoid hemorrhage: a prospective pilot study. Stroke. 2011 May;42(5):1301-6. doi: 10.1161/STROKEAHA.110.603159. Epub 2011 Mar 31.
- Muehlschlegel S, Carandang R, Hall W, Kini N, Izzy S, Garland B, Ouillette C, van der Bom IM, Flood TF, Gounis MJ, Weaver JP, Barton B, Wakhloo AK. Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial. J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):1029-35. doi: 10.1136/jnnp-2014-308778. Epub 2014 Oct 24.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Vasospasm, Intracranial
- Physiological Effects of Drugs
- Peripheral Nervous System Agents
- Natriuretic Agents
- Diuretics, Osmotic
- Diuretics
- Neuromuscular Agents
- Muscle Relaxants, Central
- Mannitol
- Dantrolene
Other Study ID Numbers
- H-13441
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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