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Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures

Phase 2
Terminated
Conditions
Febrile Seizure
Interventions
Drug: Carbogen
Drug: Placebo
Registration Number
NCT01370044
Lead Sponsor
Charite University, Berlin, Germany
Brief Summary

The aim of this clinical trail is to evaluate the efficacy of a Carbogen inhalation in patients with febrile seizures compared to a placebo-inhalation.

Further aims are the evaluation of the safety of the Carbogen inhalation via a low-pressure can with a breathing mask in a home-setting, the manageability of the Carbogen inhalation via a low pressure can with a breathing mask in a home-setting or on the way (mobility), the quality of life of the parents and children using the low pressure can with a breathing mask in a home-setting or on the way (mobility) and the contentment and anxiety of the parents.

Detailed Description

For detailed protocol see:

Ohlraun S, Wollersheim T, Weiß C, Martus P, Weber-Carstens S, Schmitz D, Schuelke M. CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study. J Transl Med. 2013 Jun 27;11:157. doi: 10.1186/1479-5876-11-157.

BACKGROUND: 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children.

METHODS: The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents.

PROSPECT: The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01370044. DOI: 10.1186/1479-5876-11-157 PMCID: PMC3700755 PMID: 23806032 \[Indexed for MEDLINE\]

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
96
Inclusion Criteria
  • condition after febrile seizure
  • age 12 months to 5 years
  • written informed consent
Exclusion Criteria
  • severe other organic disease
  • meningitis as possible cause for the cerebral seizure
  • neurologic disease or cerebral dysplasia
  • cerebrale seizures without fever in the medical history
  • hypersynchronic eeg activity
  • disorder of the respiratory tract (Asthma e.g.)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VerumCarbogenVerum arm receiving Carbogen
PlaceboPlaceboPlacebo arm receiving oxygen
Primary Outcome Measures
NameTimeMethod
number of patients which need Diazepam3 minutes

efficacy of a Carbogen inhalation in patients with febrile seizures compared to a placebo inhalation

Secondary Outcome Measures
NameTimeMethod
number of severe adverse events3 minutes

safety of the Carbogen inhalation via a low-pressure can with a breathing mask in a home-setting

manageability of the application assessed by the parents3 minutes

manageability of the Carbogen inhalation via a low pressure can with a breathing mask in a home-setting or on the way (mobility)

changes in quality of life of the parents and children after use of study medication3 minutes

quality of life of the parents and children using the low pressure can with a breathing mask in a home-setting or on the way (mobility)

contentment and anxiety of the parents10 minutes

structured interview of the parents after a seizure

Trial Locations

Locations (1)

Charite University Berlin

🇩🇪

Berlin, Germany

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