Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures

Study Overview
=================
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]

Official Title
-----------------
Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures

Conditions
-----------------
Febrile Seizure

Intervention / Treatment
-----------------
* Drug: Carbogen
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.)

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 5 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum<br>Verum arm receiving Carbogen | Drug: Carbogen<br>* 3 minutes administration of carbogen<br>* Other names: Low pressure flask with mask containing 6 L carbogen;|
| Placebo Comparator: Placebo<br>Placebo arm receiving oxygen | Drug: Placebo<br>* 3 minutes administration of oxygen<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Febrile Seizure, Carbon Dioxide, Carbogen, Respiratory Alkalosis