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NCT Number: NCT01024972

Safety Study of Dantrolene 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.

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Key information

Conditions

Subarachnoid Hemorrhage Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebral Vasospasm Cerebrovascular Disorders Hemorrhage Intracranial Hemorrhages Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases Vasospasm, Intracranial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UMASS Medical School / UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Dantrolene

Drug

Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days

Other names: Dantrium

Placebo

Drug

equiosmolar volume (5% mannitol) every 6 hours x 7 days

Other names: Free water/5% mannitol solution

Primary outcomes

  1. Hyponatremia

    Time frame: Seven days

    Number of subjects who developed hyponatremia (sNa ≤132mmol/L)

Secondary outcomes

  1. 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.

  2. In-hospital Mortality

    Time frame: up to 90 days

    Number of subjects who expired during hospitalization.

Sponsors and collaborators

Lead sponsor

University of Massachusetts, Worcester

Other

Collaborators

  • American Heart Association

Registry information

Official study title

Dantrolene in the Prevention and Treatment of Cerebral Vasospasm in Subarachnoid Hemorrhage

Important dates

Study start
2009
Primary completion
2013
Study completion
2013
First posted
Dec 3, 2009
Registry last updated
Mar 5, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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