Trial Outcomes & Findings for Safety Study of Dantrolene in Subarachnoid Hemorrhage (NCT NCT01024972)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Seven days

Results posted on

2015-03-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Dantrolene 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	Placebo 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
Overall Study STARTED	16	15
Overall Study COMPLETED	16	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety Study of Dantrolene in Subarachnoid Hemorrhage

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dantrolene n=16 Participants Intravenous Datrolene 1.25 mg/kg (includes 5% mannitol) every 6 hours for seven days.	Placebo n=15 Participants Equiosmolar volume (5% mannitol) every 6 hours for seven days.	Total n=31 Participants Total of all reporting groups
Age, Continuous	56 years STANDARD_DEVIATION 12 • n=5 Participants	52 years STANDARD_DEVIATION 11 • n=7 Participants	54 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	15 participants n=5 Participants	9 participants n=7 Participants	24 participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	0 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized African American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Seven days

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

Outcome measures

Outcome measures
Measure	Dantrolene n=16 Participants Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days	Placebo n=15 Participants equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days.
Hyponatremia	7 participants	10 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Dantrolene n=16 Participants Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days	Placebo n=15 Participants equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days.
Liver Toxicity	1 participants	0 participants

SECONDARY outcome

Timeframe: up to 90 days

Number of subjects who expired during hospitalization.

Outcome measures

Outcome measures
Measure	Dantrolene n=16 Participants Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days	Placebo n=15 Participants equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days.
In-hospital Mortality	2 participants	1 participants

Adverse Events

Dantrolene

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dantrolene n=16 participants at risk Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days	Placebo n=15 participants at risk equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days
Nervous system disorders Neurological deterioration	12.5% 2/16 • Number of events 2 • 90 days	6.7% 1/15 • Number of events 1 • 90 days
Hepatobiliary disorders Liver toxicity	6.2% 1/16 • Number of events 1 • 90 days	0.00% 0/15 • 90 days
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	12.5% 2/16 • Number of events 2 • 90 days	0.00% 0/15 • 90 days
Nervous system disorders Headache	0.00% 0/16 • 90 days	6.7% 1/15 • Number of events 1 • 90 days
General disorders Drug administration error	0.00% 0/16 • 90 days	6.7% 1/15 • Number of events 1 • 90 days

Other adverse events

Other adverse events
Measure	Dantrolene n=16 participants at risk Dantrolene 1.25mg/kg IV (includes 5% mannitol) every 6 hours x 7 days	Placebo n=15 participants at risk equiosmolar, volume-equivalent sterile water with 5% mannitol every 6 hours x 7 days
Vascular disorders Venous infiltration	25.0% 4/16 • Number of events 4 • 90 days	0.00% 0/15 • 90 days
Gastrointestinal disorders Nausea/vomiting	18.8% 3/16 • Number of events 3 • 90 days	6.7% 1/15 • Number of events 1 • 90 days
Nervous system disorders Headache	12.5% 2/16 • Number of events 2 • 90 days	0.00% 0/15 • 90 days
Renal and urinary disorders Urinary tract infection	6.2% 1/16 • Number of events 1 • 90 days	0.00% 0/15 • 90 days
Cardiac disorders Myocardial Infarction	6.2% 1/16 • Number of events 1 • 90 days	0.00% 0/15 • 90 days
Gastrointestinal disorders Constipation	6.2% 1/16 • Number of events 1 • 90 days	0.00% 0/15 • 90 days

Additional Information

Dr. Susanne Muehlschlegel

University of Massachusetts Medical School

Phone: 508-421-5500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place