Safety Study of Dantrolene in Subarachnoid Hemorrhage

February 18, 2015 updated by: University of Massachusetts, Worcester

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • UMASS Medical School / UMass Memorial Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / 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 Names:
  • Dantrium
PLACEBO_COMPARATOR: Placebo
Equiosmolar volume (5% Mannitol)
Drug: Placebo
equiosmolar volume (5% mannitol) every 6 hours x 7 days
Other Names:
  • Free water/5% mannitol solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hyponatremia
Time Frame: Seven days
Number of subjects who developed hyponatremia (sNa ≤132mmol/L)
Seven days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
7 days
In-hospital Mortality
Time Frame: up to 90 days
Number of subjects who expired during hospitalization.
up to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Massachusetts, Worcester

Collaborators

American Heart Association

Investigators

  • Principal Investigator: Susanne Muehlschlegel, MD, University of Massachusetts, Worcester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (ACTUAL)

July 1, 2013

Study Completion (ACTUAL)

October 1, 2013

Study Registration Dates

First Submitted

December 1, 2009

First Submitted That Met QC Criteria

December 1, 2009

First Posted (ESTIMATE)

December 3, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

March 5, 2015

Last Update Submitted That Met QC Criteria

February 18, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-13441

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Subarachnoid Hemorrhage

Clinical Trials on Dantrolene

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe