Dantrolene for Treatment of Hyperthermia in Subarachnoidal Hemorrhage (SAH) (DTH1)

This study has been terminated.
(organizationally not possible)
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00796900
First received: November 20, 2008
Last updated: May 11, 2011
Last verified: September 2009

November 20, 2008
May 11, 2011
May 2008
March 2011   (final data collection date for primary outcome measure)
Magnitude and Duration of Hyperthermia [ Time Frame: 8 hours, every 10 minutes ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00796900 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Dantrolene for Treatment of Hyperthermia in Subarachnoidal Hemorrhage (SAH)
Dantrolene as a Treatment for Hyperthermia in Patients After Subarachnoidal Hemorrhage

Dantrolene is used to prevent hyperthermia in intensive care patients suffering from subarachnoidal hemorrhage.

Background:

Fever episodes occur in more than 50% of patients admitted to the ICU for subarachnoidal hemorrhage, central nervous system infection, seizure control, hemorrhagic stroke, and closed head injury despite antibiotic and antipyretic therapy.

The exact mechanism of hyperthermia-induced brain injury is not known; however, various processes may be involved. For example, hyperthermia might increase the release of excitatory neurotransmitter or trigger an abundant amount of oxygen free radicals. Hyperthermia may also aggravate blood-brain barrier disruption, impair cytoskeletal proteolysis, and/or enhance inhibition of enzymatic protein kinases, which, in turn, would impair recovery of energy metabolism. Antipyretics are effective for conventional fever, but less useful for various central hyperthermia syndromes, especially those resulting from strokes, SAH, and head injuries. Even aggressive cooling is usually insufficient in patients with fever because it is unable to overcome the high metabolic rate in these patients. Likewise, physical cooling is counteracted by the thermoregulatory defenses being activated to maintain hyperthermia. In non-sedated individuals, active cooling increases metabolic stress without decreasing core temperature at all. To date, treatment of centrally mediated hyperthermia remains unsatisfying.

Dantrolene has been available since 1975 as a specific treatment for acute malignant hyperthermia crises. However, dantrolene is increasingly being used for emergency treatment of life-threatening hyperthermia that is unresponsive to conventional treatments. For example, the drug has been used with some success for acute treatment of life-threatening hyperthermia resulting from neuroleptic malignant syndrome and hyperthermia associated with overdoses of various drugs. It has also been used for treatment of various other types of hyperthermia.

Efficacy in these cases appears to be based on a non-specific action of the drug; but to the extent dantrolene is effective, its action must conform to the laws of thermodynamics. Dantrolene must, therefore, reduce metabolic heat production, augment systemic heat loss, or alter the normal distribution of heat within the body. In other words, dantrolene must reverse the abnormal (or ineffective) thermoregulatory control that initiates the hyperthermic crises.

Item:

We propose to test the hypothesis that dantrolene will reduce centrally mediated fever in patients after subarachnoidal hemorrhage. Specifically, we will test the hypothesis that dantrolene decreases the magnitude and duration of hyperthermia.

The study will be restricted to neurosurgical patients with sustained fever (≥38ºC for more than an hour) without an identifiable infectious cause after subarachnoidal hemorrhage aged from 18 to 80 years. There will be no limitation of enrollment as to patients breathing spontaneously or being ventilator dependant.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Hyperthermia
  • Drug: Dantrolene
    Patients who satisfy the inclusion/exclusion criteria of the study and who are enrolled in this study will be randomized with computer-generated grouping to either one of two groups. One group of subjects will be given dantrolene for the first episode of fever. The other group will be given placebo. Dantrolene is supplied in 70-ml vials containing 20 mg dantrolene. Dantrolene will be given in the following dose: 5 mg/kg BW given intravenously over 30 minutes. As placebo NaCl 0,9% will be used.
  • Drug: Placebo
    Patients who satisfy the inclusion/exclusion criteria of the study and who are enrolled in this study will be randomized with computer-generated grouping to either one of two groups. One group of subjects will be given dantrolene for the first episode of fever. The other group will be given placebo. Dantrolene is supplied in 70-ml vials containing 20 mg dantrolene. Dantrolene will be given in the following dose: 5 mg/kg BW given intravenously over 30 minutes. As placebo NaCl 0,9% will be used.
  • Experimental: Dantrolene
    Intervention: Drug: Dantrolene
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
34
March 2011
March 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • neurosurgical patients after subarachnoidal hemorrhage
  • breathing spontaneously or being ventilator dependant
  • sustained fever (≥38ºC for more than an hour) without an identifiable infectious cause.

Exclusion Criteria:

  • infection
  • pregnancy
  • arrhythmia
  • muscular dystrophia
  • acute liver disease
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Austria
 
NCT00796900
EK 197/2004
No
Andrea Holzer, MD, Medical University Vienna
Medical University of Vienna
Not Provided
Principal Investigator: Andrea Holzer, MD Medical University Vienna, Department of Anesthesiology and General Intensive Care Medicine
Medical University of Vienna
September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP