Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Text Size

Safety Study of Dantrolene in Subarachnoid Hemorrhage

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT01024972
First received: December 1, 2009
Last updated: February 18, 2015
Last verified: February 2015
History of Changes

December 1, 2009
February 18, 2015
October 2009
July 2013   (final data collection date for primary outcome measure)
Hyponatremia [ Time Frame: Seven days ] [ Designated as safety issue: Yes ]
Number of subjects who developed hyponatremia (sNa ≤132mmol/L)
- Tolerability - Hyponatremia [ Time Frame: Seven days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01024972 on ClinicalTrials.gov Archive Site
  • 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.
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 ]
Not Provided
Not Provided
 
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.
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.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Subarachnoid Hemorrhage
  • Cerebral Vasospasm
  • 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
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
October 2013
July 2013   (final data collection date for primary outcome measure)

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)
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01024972
H-13441
Yes
Not Provided
Not Provided
University of Massachusetts, Worcester
University of Massachusetts, Worcester
American Heart Association
Principal Investigator: Susanne Muehlschlegel, MD University of Massachusetts, Worcester
University of Massachusetts, Worcester
February 2015

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