Safety Study of Dantrolene in Subarachnoid Hemorrhage
| Status: | Completed |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 11/18/2012 |
| Start Date: | October 2009 |
| End Date: | October 2012 |
| Contact: | Cindy Ouillette, RN |
| Email: | Cynthia.Ouillette@umassmed.edu |
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, 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.
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)
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