← Back
NeuroTrials.ai
Neurology Clinical Trial Database

Dantrolene SAH Trial

Dantrolene for the Prevention and Treatment of Cerebral Vasospasm After Subarachnoid Hemorrhage - a Randomized Placebo-Controlled Trial to assess Safety, Tolerability and Feasibility

Share Share Copied! Compare

Year of Publication: 2014

Authors: Susanne Muehlschlegel, Raphael A. Carandang, Wiley R. Hall, ..., Bruce A. Barton

Journal: Stroke

Citation: Stroke. 2014 May; DOI: 10.1161/str.45.suppl_1.tp352

PDF: https://www.researchgate.net/profile/Sus...saWNhdGlvbiJ9fQ

Clinical Question

Is intravenous dantrolene safe, tolerable and feasible for prevention and treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage?

Bottom Line

In this small pilot trial of 31 patients, intravenous dantrolene after aneurysmal SAH was feasible, tolerable and safe, with no significant differences in primary safety outcomes (hyponatremia or liver toxicity). The study was underpowered to show efficacy or outcome differences, though quantitative angiogram analysis revealed a trend toward increased vessel diameters in the dantrolene group.

Major Points

  • Single-center, randomized, double-blind, placebo-controlled pilot trial in 31 aSAH patients
  • Primary safety endpoints (hyponatremia and liver toxicity) showed no significant differences between groups
  • Hyponatremia occurred in 44% dantrolene vs 67% placebo (p=0.29); liver toxicity in 6% vs 0% (p=1.0)
  • Numerically more adverse events in dantrolene group but not statistically significant (16 vs 5 AEs, RR 2.2, 95% CI 0.7-6.7, p=0.16)
  • Five patients (3 dantrolene, 2 placebo) reached stop criteria
  • No significant differences in angiographic, TCD, or clinical vasospasm occurrence
  • No differences in delayed cerebral ischemia or 3-month functional outcomes
  • Quantitative angiogram analysis showed trend toward increased vessel diameters after 7-day infusion in dantrolene group (p=0.05)
  • Study was underpowered to demonstrate efficacy

Design

Study Type: Single-center, randomized, double-blind, placebo-controlled pilot trial

Randomization: 1

Blinding: Double-blind

Follow-up Duration: 3 months

Centers: 1

Countries: United States

Sample Size: 31

Analysis: Non-parametric tests, generalized estimating equations, and mixed models

Inclusion Criteria

  • Acute aneurysmal subarachnoid hemorrhage

Baseline Characteristics

CharacteristicControlActive

Arms

FieldDantroleneControl
InterventionIntravenous dantrolene 1.25 mg every 6 hours for 7 daysPlacebo infusion every 6 hours for 7 days
Duration7 days7 days

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of hyponatremia (serum sodium ≤134 mmol/L) and liver toxicity (percentage of patients with ALT, AST and alkaline phosphatase >5x upper limit of normal)PrimaryHyponatremia: 67%; Liver toxicity: 0%Hyponatremia: 44%; Liver toxicity: 6%23.00%Hyponatremia p=0.29; Liver toxicity p=1.0
Adverse events (AEs)Secondary5 AEs total, 2 severe16 AEs total, 5 severeRR 2.2p=0.16, 95% CI 0.7-6.7
Patients reaching stop criteriaSecondary2 patients (brain edema requiring osmotherapy)3 patients (1 liver toxicity, 2 brain edema requiring osmotherapy)
Angiographic vasospasmSecondaryNo significant differences
Transcranial Doppler (TCD) vasospasmSecondaryNo significant differences
Clinical vasospasmSecondaryNo significant differences
Delayed cerebral ischemia (DCI)SecondaryNo significant differences
Quantitative angiogram - vessel diameters after 7-day infusionSecondaryTrend toward increased vessel diameters in dantrolene groupp=0.05
3-month modified Rankin ScaleSecondaryNo significant differences
3-month Glasgow Outcome ScaleSecondaryNo significant differences
3-month Barthel IndexSecondaryNo significant differences
Total adverse eventsAdverse5 AEs16 AEsRR 2.2 (95% CI 0.7-6.7)p=0.16
Severe adverse eventsAdverse25
HyponatremiaAdverse67%44%p=0.29
Liver toxicityAdverse0%6%p=1.0
Brain edema requiring osmotherapyAdverse2 patients2 patients

Criticisms

  • Very small sample size (n=31 total, 16 dantrolene vs 15 placebo) - pilot study
  • Underpowered to detect efficacy or outcome differences
  • Single-center study limiting generalizability
  • No detailed baseline characteristics provided in abstract
  • Incomplete inclusion/exclusion criteria listed
  • Limited data on specific types of vasospasm assessments
  • Numerically higher adverse events in treatment group though not statistically significant
  • Only abstract/poster presentation available, not full manuscript
  • Trend toward increased vessel diameters (p=0.05) requires confirmation in larger trial
  • 3-month follow-up may be insufficient for long-term outcomes

Funding

American Heart Association (Scientist Development Grant 09SDG2030022); Worcester Research Foundation (2010 Award); University of Massachusetts Medical School (Faculty Scholar Award); University of Massachusetts Center for Clinical & Translational Science/CTSA (UL1TR000161). Study drug dantrolene (Dantrium IV) donated by J.H.P. Pharmaceuticals (Parsippany, NJ). Study was entirely investigator-initiated.

Based on: Dantrolene SAH Trial (Stroke, 2014)

Authors: Susanne Muehlschlegel, Raphael A. Carandang, Wiley R. Hall, ..., Bruce A. Barton

Citation: Stroke. 2014 May; DOI: 10.1161/str.45.suppl_1.tp352

Content summarized and formatted by NeuroTrials.ai.