CARDIF: Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures

Sponsor

Charite University, Berlin, Germany (Other)

Overall Status

Terminated

CT.gov ID

NCT01370044

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Febrile Seizure	Drug: Carbogen Drug: Placebo	Phase 2/Phase 3

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]

Study Design

Study Type:

Interventional

Actual Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures

Study Start Date :

Aug 1, 2012

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Verum Verum arm receiving Carbogen	Drug: Carbogen 3 minutes administration of carbogen Other Names: Low pressure flask with mask containing 6 L carbogen
Placebo Comparator: Placebo Placebo arm receiving oxygen	Drug: Placebo 3 minutes administration of oxygen Other Names: Low pressure flask with mask containing 6 L oxygen

Arm

Intervention/Treatment

Experimental: Verum

Verum arm receiving Carbogen

Drug: Carbogen

3 minutes administration of carbogen

Other Names:

Low pressure flask with mask containing 6 L carbogen

Placebo Comparator: Placebo

Placebo arm receiving oxygen

Drug: Placebo

3 minutes administration of oxygen

Other Names:

Low pressure flask with mask containing 6 L oxygen

Outcome Measures

Primary Outcome Measures

number of patients which need Diazepam [3 minutes]
efficacy of a Carbogen inhalation in patients with febrile seizures compared to a placebo inhalation

Secondary Outcome Measures

number of severe adverse events [3 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 parents [3 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 medication [3 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 parents [10 minutes]
structured interview of the parents after a seizure