Dantrolene for Treatment of Hyperthermia in Subarachnoidal Hemorrhage (SAH)

NCT ID: NCT00796900

Last Updated: 2011-05-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2011-03-31

Brief Summary

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

Detailed Description

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.

Conditions

Hyperthermia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dantrolene

Group Type: EXPERIMENTAL

Dantrolene

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Medical University Vienna

Principal Investigators

Andrea Holzer, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna, Department of Anesthesiology and General Intensive Care Medicine

Locations

Medical University Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

EK 197/2004

Identifier Type: -

Identifier Source: org_study_id