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Phase 2 N=10 Treatment

Safety Study of Dantrolene to Treat Cerebral Vasospasm After Subarachnoid Hemorrhage

Cerebral Vasospasm After Subarachnoid Hemorrhage

Enrolled (actual)
10
Serious AEs
10.0%
Results posted
May 2012
Primary outcome: Primary: Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion) — -8; -3.4 mmHg

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Dantrolene (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
University of Massachusetts, Worcester
Primary completion
Oct 2009

Outcome Measures

OutcomeResultp-value
PRIMARY
Hemodynamic Parameters (Change From Baseline Systolic Blood Pressure (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
-8; -3.4
SECONDARY
Transcranial Doppler Peak Systolic Velocity (Change From Baseline Peak Systolic Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
-30; -26
SECONDARY
Transcranial Doppler Mean Flow Velocity (Change From Baseline Mean Flow Velocity (Pre-infusion) Over Time Until 135 Minutes Post-infusion)
-18; -13

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. Therefore, we plan to undertake this study to evaluate the safety and tolerability of treatment with dantrolene in patients with cVSP after SAH, and to determine the maximal tolerated dose to be used in future studies to determine if treatment with Dantrolene can improve the outcome of patients with cVSP after SAH.

Eligibility Criteria

Inclusion Criteria

  • Participants with aneurysmal SAH admitted to the Massachusetts General Hospital NeuroICU (Blake 12) and undergoing standard-of-care daily transcranial doppler (TCD).
  • Participants with unilateral or bilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), or basilar artery vasospasm as defined by the following TCD criteria
  • a >50% mean velocity increase from the baseline mean TCD velocity (baseline is the first TCD measurement, usually within 24hrs of admission), or
  • peak systolic TCD velocities of 200 cm/s or higher in the MCA or ACA (for MCA with a concurrent ipsilateral LR of 3.0 or higher), or peak systolic TCD velocities of 120 cm/s or higher in the PCA or basilar artery, or
  • any daily 100 cm/s peak systolic TCD velocity increase from the previous day, or
  • any longitudinal mean TCD velocity increase of 80 cm/s or more

Exclusion Criteria

  • Inability to obtain consent from patient or health care proxy
  • Age 165 Units/L, AST >120 Units/L, alkaline phosphatase >345 Units/L (three times upper limit of normal)
  • Participants on verapamil
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00964548). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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