HyperthermiaPhase 2/3DTH1NCT00796900
Dantrolene for Treatment of Hyperthermia in Subarachnoidal Hemorrhage (SAH)
A Phase 2/3 study testing Dantrolene in people with Hyperthermia, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Dantrolene is used to prevent hyperthermia in intensive care patients suffering from subarachnoidal hemorrhage. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hyperthermia
- What is being tested?
- Dantrolene
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteAustria
- Study dates
- May 2008to Mar 2011
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- neurosurgical patients after subarachnoidal hemorrhage
- breathing spontaneously or being ventilator dependant
- sustained fever (≥38ºC for more than an hour) without an identifiable infectious cause.
Who cannot join
- infection
- pregnancy
- arrhythmia
- muscular dystrophia
- acute liver disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Dantrolene, Placebo
- Keywords
- Hyperthermia, subarachnoidal hemorrhage, placebo controlled, double blinded, Dantrolene
- Medical subject headings
- Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DantroleneDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dantrolene | Experimental | Not described Receives: Drug: Dantrolene |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Magnitude and Duration of Hyperthermia
Measured: 8 hours, every 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2008 (estimated)
- Study startMay 2008
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: organizationally not possible
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperthermiaStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Investigators
- Andrea Holzer, MD, Principal investigator, Medical University Vienna, Department of Anesthesiology and General Intensive Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00796900
- Sponsor's protocol ID
- EK 197/2004
- Acronym
- DTH1
- Status last verified
- Sep 2009
- First submitted
- 20 Nov 2008
- Last updated
- 12 May 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dantrolene as a Treatment for Hyperthermia in Patients After Subarachnoidal Hemorrhage
- ClinicalTrials.gov ID
- NCT00796900
- Acronym / sponsor ID
- DTH1 / EK 197/2004
- Conditions
- Hyperthermia
- Keywords
- Hyperthermia, subarachnoidal hemorrhage, placebo controlled, double blinded, Dantrolene
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: organizationally not possible
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 24 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dantrolene | Experimental | Drug: Dantrolene |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- neurosurgical patients after subarachnoidal hemorrhage
- breathing spontaneously or being ventilator dependant
- sustained fever (≥38ºC for more than an hour) without an identifiable infectious cause.
Key exclusion criteria (5 listed)
- infection
- pregnancy
- arrhythmia
- muscular dystrophia
- acute liver disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DantrolenePatients 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 | Dantrolene |
| PlaceboPatients 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 |
Primary outcome
Magnitude and Duration of Hyperthermia
Time frame: 8 hours, every 10 minutes
Results and safety
The study was stopped early (reason given: organizationally not possible). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Holzer, MD principal investigator
Medical University Vienna, Department of Anesthesiology and General Intensive Care Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dantrolene in people with Hyperthermia, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: organizationally not possible). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnitude and Duration of Hyperthermia (time frame: 8 hours, every 10 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2011.