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

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.

Study Overview

• Status: Terminated
• Conditions: Febrile Seizure
• Intervention / Treatment: Drug: Carbogen; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10107
    • Charité University Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients which need Diazepam	efficacy of a Carbogen inhalation in patients with febrile seizures compared to a placebo inhalation	3 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of severe adverse events	safety of the Carbogen inhalation via a low-pressure can with a breathing mask in a home-setting	3 minutes
manageability of the application assessed by the parents	manageability of the Carbogen inhalation via a low pressure can with a breathing mask in a home-setting or on the way (mobility)	3 minutes
changes in quality of life of the parents and children after use of study medication	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)	3 minutes
contentment and anxiety of the parents	structured interview of the parents after a seizure	10 minutes

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Markus Schülke-Gerstenfeld, Charite - NeuroCure

Publications and helpful links

General Publications

• 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.

Helpful Links

• Homepage of the NeuroCure Clinical Resaerch Center at the Charité Berlin

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: May 20, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 9, 2011

Study Record Updates

• Last Update Posted (Actual): January 26, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Carbon Dioxide; Respiratory Alkalosis; Febrile Seizure; Carbogen
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Seizures; Hyperthermia; Fever; Seizures, Febrile
• Other Study ID Numbers: CARDIF