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Safety Study of Dantrolene in Subarachnoid Hemorrhage

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ClinicalTrials.gov Identifier: NCT01024972
Recruitment Status : Completed
First Posted : December 3, 2009
Results First Posted : March 5, 2015
Last Update Posted : March 5, 2015
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
University of Massachusetts, Worcester

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Subarachnoid Hemorrhage
Cerebral Vasospasm
Interventions Drug: Dantrolene
Drug: Placebo
Enrollment 31
Recruitment Details All patients with aSAH were screened for eligibility between 10/2009 and 10/2012. Inclusion criteria were aSAH ≥18 years, aneurysm fully secured by coiling or clipping, Hunt&Hess grade <5, modified Fisher Scale >1, ALT, AST, AlkPhos <3x upper limit of normal, serum Na (sNa) ≥135mmol/L and no mannitol or hypertonic saline prior to drug infusion.
Pre-assignment Details Routine patient management: All aSAH patients were treated according to our institutional protocol following published aSAH critical care guidelines, including admission to our closed neuroscience intensive care unit (neuroICU) with board-certified neurointensivist as the primary attending.
Arm/Group Title Dantrolene Placebo
Hide Arm/Group Description

Dantrolene 1.25mg/kg IV every 6 hours x 7 days

Dantrolene vs. Placebo: Dantrolene 1.25mg/kg IV (includes 5% mannitol) or equiosmolar placebo (5% mannitol) every 6 hours x 7 days

Equiosmolar volume (5% Mannitol)

Dantrolene vs. Placebo: Dantrolene 1.25mg/kg IV (includes 5% mannitol) or equiosmolar placebo (5% mannitol) every 6 hours x 7 days

Period Title: Overall Study
Started 16 15
Completed 16 15
Not Completed 0 0
Arm/Group Title Dantrolene Placebo Total
Hide Arm/Group Description Intravenous Datrolene 1.25 mg/kg (includes 5% mannitol) every 6 hours for seven days. Equiosmolar volume (5% mannitol) every 6 hours for seven days. Total of all reporting groups
Overall Number of Baseline Participants 16 15 31
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 15 participants 31 participants
56  (12) 52  (11) 54  (12)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 31 participants
Female
14
  87.5%
12
  80.0%
26
  83.9%
Male
2
  12.5%
3
  20.0%
5
  16.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 15 participants 31 participants
White 15 9 24
Hispanic/Latino 0 6 6
African American 1 0 1
1.Primary Outcome
Title Hyponatremia
Hide Description Number of subjects who developed hyponatremia (sNa ≤132mmol/L)
Time Frame Seven days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dantrolene Placebo
Hide Arm/Group Description:
Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days
equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days.
Overall Number of Participants Analyzed 16 15
Measure Type: Number
Unit of Measure: participants
7 10
2.Secondary Outcome
Title Liver Toxicity
Hide Description Number of subjects who developed liver toxicity as evidenced by Liver Function Test elevation greater than 5 times the upper limit of normal.
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dantrolene Placebo
Hide Arm/Group Description:
Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days
equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days
Overall Number of Participants Analyzed 16 15
Measure Type: Number
Unit of Measure: participants
1 0
3.Secondary Outcome
Title In-hospital Mortality
Hide Description Number of subjects who expired during hospitalization.
Time Frame up to 90 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dantrolene Placebo
Hide Arm/Group Description:
Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days
equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days
Overall Number of Participants Analyzed 16 15
Measure Type: Number
Unit of Measure: participants
2 1
Time Frame 90 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dantrolene Placebo
Hide Arm/Group Description Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days
All-Cause Mortality
Dantrolene Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Dantrolene Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/16 (25.00%)      2/15 (13.33%)    
General disorders     
Drug administration error *  0/16 (0.00%)  0 1/15 (6.67%)  1
Hepatobiliary disorders     
Liver toxicity * [1]  1/16 (6.25%)  1 0/15 (0.00%)  0
Nervous system disorders     
Neurological deterioration * [2]  2/16 (12.50%)  2 1/15 (6.67%)  1
Headache *  0/16 (0.00%)  0 1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure *  2/16 (12.50%)  2 0/15 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Liver function test elevation greater than 5 times upper limit of normal
[2]
Neurological deterioration requiring osmotherapy
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dantrolene Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/16 (75.00%)      1/15 (6.67%)    
Cardiac disorders     
Myocardial Infarction  [1]  1/16 (6.25%)  1 0/15 (0.00%)  0
Gastrointestinal disorders     
Nausea/vomiting *  3/16 (18.75%)  3 1/15 (6.67%)  1
Constipation *  1/16 (6.25%)  1 0/15 (0.00%)  0
Nervous system disorders     
Headache *  2/16 (12.50%)  2 0/15 (0.00%)  0
Renal and urinary disorders     
Urinary tract infection *  1/16 (6.25%)  1 0/15 (0.00%)  0
Vascular disorders     
Venous infiltration *  4/16 (25.00%)  4 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
[1]
Non-(ST wave)-elevation myocardial infarction
Placebo group consisted of free water with 5% mannitol to achieve the same equiosmolar solution as IV-D which requires reconstitution in free water. Unable to differentiate whether hyponatremia or brain oedema was due to IV-D or its solution.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Susanne Muehlschlegel
Organization: University of Massachusetts Medical School
Phone: 508-421-5500
EMail: susanne.muehlschlegel@umassmemorial.org
Layout table for additonal information
Responsible Party: University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT01024972    
Other Study ID Numbers: H-13441
First Submitted: December 1, 2009
First Posted: December 3, 2009
Results First Submitted: January 2, 2015
Results First Posted: March 5, 2015
Last Update Posted: March 5, 2015