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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

Tracking Information
First Submitted Date  ICMJE December 1, 2009
First Posted Date  ICMJE December 3, 2009
Results First Submitted Date  ICMJE January 2, 2015
Results First Posted Date  ICMJE March 5, 2015
Last Update Posted Date March 5, 2015
Study Start Date  ICMJE October 2009
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2015)
Hyponatremia [ Time Frame: Seven days ]
Number of subjects who developed hyponatremia (sNa ≤132mmol/L)
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
- Tolerability - Hyponatremia [ Time Frame: Seven days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2015)
  • 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.
  • In-hospital Mortality [ Time Frame: up to 90 days ]
    Number of subjects who expired during hospitalization.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Dantrolene in Subarachnoid Hemorrhage
Official Title  ICMJE Dantrolene in the Prevention and Treatment of Cerebral Vasospasm in Subarachnoid Hemorrhage
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Subarachnoid Hemorrhage
  • Cerebral Vasospasm
Intervention  ICMJE
  • Drug: Dantrolene
    Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days
    Other Name: Dantrium
  • Drug: Placebo
    equiosmolar volume (5% mannitol) every 6 hours x 7 days
    Other Name: Free water/5% mannitol solution
Study Arms  ICMJE
  • Experimental: Dantrolene
    Dantrolene 1.25mg/kg IV every 6 hours x 7 days
    Intervention: Drug: Dantrolene
  • Placebo Comparator: Placebo
    Equiosmolar volume (5% Mannitol)
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2015)
31
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2009)
30
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01024972
Other Study ID Numbers  ICMJE H-13441
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Massachusetts, Worcester
Study Sponsor  ICMJE University of Massachusetts, Worcester
Collaborators  ICMJE American Heart Association
Investigators  ICMJE
Principal Investigator: Susanne Muehlschlegel, MD University of Massachusetts, Worcester
PRS Account University of Massachusetts, Worcester
Verification Date February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP