Safety Study of Dantrolene in Subarachnoid Hemorrhage

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Susanne Muehlschlegel, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT01024972
First received: December 1, 2009
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Subarachnoid Hemorrhage
Cerebral Vasospasm
Drug: Dantrolene vs. Placebo
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:
  • - Tolerability - Hyponatremia [ Time Frame: Seven days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Liver toxicity; hemodynamic measures; intracranial pressure; change in daily TCD velocities from baseline; number of required intraarterial vasospasm treatments; degree of angiographic vasospasm; outcome trends at 90 days assessed by GOS, mRS and BI. [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: October 2009
Study Completion Date: October 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dantrolene
Dantrolene 1.25mg/kg IV every 6 hours x 7 days
Drug: Dantrolene vs. Placebo
Dantrolene 1.25mg/kg IV (includes 5% mannitol) or equiosmolar placebo (5% mannitol) every 6 hours x 7 days
Other Name: Dantrium
Placebo Comparator: Placebo
Equiosmolar volume (5% Mannitol)
Drug: Dantrolene vs. Placebo
Dantrolene 1.25mg/kg IV (includes 5% mannitol) or equiosmolar placebo (5% mannitol) every 6 hours x 7 days
Other Name: Dantrium

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, AST, ALT and 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented aneurysmal SAH by CTA, 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01024972

Locations
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
Principal Investigator: Susanne Muehlschlegel, MD University of Massachusetts, Worcester
  More Information

Publications:
Responsible Party: Susanne Muehlschlegel, Study Principal Investigator, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT01024972     History of Changes
Other Study ID Numbers: H-13441
Study First Received: December 1, 2009
Last Updated: December 17, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Vasospasm, Intracranial
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Dantrolene
Muscle Relaxants, Central
Physiological Effects of Drugs
Pharmacologic Actions
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014