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

History of Changes

Tracking Information

First Received Date ^ICMJE

December 1, 2009

Last Updated Date

December 17, 2013

Start Date ^ICMJE

October 2009

Primary Completion Date

July 2013 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

- Tolerability - Hyponatremia [ Time Frame: Seven days ] [ Designated as safety issue: Yes ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT01024972 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

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, 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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Subarachnoid Hemorrhage
Cerebral Vasospasm

Intervention ^ICMJE

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

Study Arm (s)

Experimental: Dantrolene
Dantrolene 1.25mg/kg IV every 6 hours x 7 days

Intervention: Drug: Dantrolene vs. Placebo
Placebo Comparator: Placebo
Equiosmolar volume (5% Mannitol)

Intervention: Drug: Dantrolene vs. 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

Enrollment ^ICMJE

Completion Date

October 2013

Primary Completion Date

July 2013 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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)

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

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

Responsible Party

Susanne Muehlschlegel, 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

Information Provided By

University of Massachusetts, Worcester

Verification Date

December 2013

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

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