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Safety Study of Dantrolene in Subarachnoid Hemorrhage

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ClinicalTrials.gov Identifier: NCT01024972
Recruitment Status : Completed
First Posted : December 3, 2009
Results First Posted : March 5, 2015
Last Update Posted : March 5, 2015
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
University of Massachusetts, Worcester

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Subarachnoid Hemorrhage Cerebral Vasospasm Drug: Dantrolene Drug: Placebo Phase 1 Phase 2

Detailed Description:
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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dantrolene in the Prevention and Treatment of Cerebral Vasospasm in Subarachnoid Hemorrhage
Study Start Date : October 2009
Actual Primary Completion Date : July 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dantrolene
Dantrolene 1.25mg/kg IV every 6 hours x 7 days
 Drug: Dantrolene
Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days
Other Name: Dantrium
Placebo Comparator: Placebo
Equiosmolar volume (5% Mannitol)
 Drug: Placebo
equiosmolar volume (5% mannitol) every 6 hours x 7 days
Other Name: Free water/5% mannitol solution


Outcome Measures
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Primary Outcome Measures :
  1. Hyponatremia [ Time Frame: Seven days ]
    Number of subjects who developed hyponatremia (sNa ≤132mmol/L)


Secondary Outcome Measures :
  1. 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.

  2. In-hospital Mortality [ Time Frame: up to 90 days ]
    Number of subjects who expired during hospitalization.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01024972


Locations
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United States, Massachusetts
UMASS Medical School / UMass Memorial Medical Center
Worcester, Massachusetts, United States, 01655
Sponsors and Collaborators
University of Massachusetts, Worcester
American Heart Association
Investigators
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Principal Investigator: Susanne Muehlschlegel, MD University of Massachusetts, Worcester
More Information
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Publications of Results:

Other Publications:

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Responsible Party: University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT01024972    
Other Study ID Numbers: H-13441
First Posted: December 3, 2009    Key Record Dates
Results First Posted: March 5, 2015
Last Update Posted: March 5, 2015
Last Verified: February 2015
Additional relevant MeSH terms:
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Subarachnoid Hemorrhage
Vasospasm, Intracranial
Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
 Cardiovascular Diseases
Mannitol
Dantrolene
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Muscle Relaxants, Central
Neuromuscular Agents
Peripheral Nervous System Agents