Febrile SeizurePhase 2/3CARDIFNCT01370044
Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures
A Phase 2/3 study testing Carbogen in people with Febrile Seizure, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 months to 5 years
- Conditions the study is for
- Febrile Seizure
- What is being tested?
- Carbogen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2012to Jun 2015
- 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 12 months to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- condition after febrile seizure
- age 12 months to 5 years
- written informed consent
Who cannot join
- 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.)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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]
- Conditions
- Febrile Seizure
- Being tested
- Carbogen, Placebo
- Keywords
- Febrile Seizure, Carbon Dioxide, Carbogen, Respiratory Alkalosis
- Medical subject headings
- Seizures, Febrile, Alkalosis, Respiratory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbogenDrug
Also called Low pressure flask with mask containing 6 L carbogen
3 minutes administration of carbogen
PlaceboDrug
Also called Low pressure flask with mask containing 6 L oxygen
3 minutes administration of oxygen
| Study group | Role | What they receive |
|---|---|---|
| Verum | Experimental | Verum arm receiving Carbogen Receives: Drug: Carbogen |
| Placebo | Placebo comparator | Placebo arm receiving oxygen Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patients which need Diazepam
efficacy of a Carbogen inhalation in patients with febrile seizures compared to a placebo inhalation
Measured: 3 minutes
Secondary outcomes (4)
number of severe adverse events
safety of the Carbogen inhalation via a low-pressure can with a breathing mask in a home-setting
Measured: 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)
Measured: 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)
Measured: 3 minutes
contentment and anxiety of the parents
structured interview of the parents after a seizure
Measured: 10 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2011 (estimated)
- Study startAug 2012
- Primary completionJun 2015
- Study completionJun 2015
Why it stopped: results of interim analysis (not safety relevant)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Febrile SeizureStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markus Schuelke, M.D., Charite University, Berlin, Germany
- Investigators
- Markus Schülke-Gerstenfeld, Principal investigator, Charite - NeuroCure
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01370044
- Sponsor's protocol ID
- CARDIF
- Acronym
- CARDIF
- Status last verified
- Jan 2018
- First submitted
- 20 May 2011
- Last updated
- 26 Jan 2018
- Results posted
- No
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.
PubMed 23806032Weiss C, Hucko A, Muller-Ohlraun S, Marschenz S, Martus P, Schmitz D, Schuelke M. The use of carbogen for interruption of febrile seizures - the randomized controlled CARDIF trial. PLoS One. 2025 Dec 23;20(12):e0324422. doi: 10.1371/journal.pone.0324422. eCollection 2025.
PubMed 41433250
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carbon Dioxide (Carbogen) for the Treatment of Febrile Seizures
- ClinicalTrials.gov ID
- NCT01370044
- Acronym / sponsor ID
- CARDIF / CARDIF
- Conditions
- Febrile Seizure
- Keywords
- Febrile Seizure, Carbon Dioxide, Carbogen, Respiratory Alkalosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: results of interim analysis (not safety relevant)
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 9 Jun 2011 (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.
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]
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Verum | Experimental | Drug: CarbogenVerum arm receiving Carbogen |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo arm receiving oxygen |
Who may qualify
- Ages
- 12 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- condition after febrile seizure
- age 12 months to 5 years
- written informed consent
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| CarbogenAlso: Low pressure flask with mask containing 6 L carbogen3 minutes administration of carbogen | Drug | Verum |
| PlaceboAlso: Low pressure flask with mask containing 6 L oxygen3 minutes administration of oxygen | Drug | Placebo |
Primary outcome
number of patients which need Diazepam
Time frame: 3 minutes
efficacy of a Carbogen inhalation in patients with febrile seizures compared to a placebo inhalation
4 secondary outcomes
number of severe adverse events
Time frame: 3 minutes
manageability of the application assessed by the parents
Time frame: 3 minutes
changes in quality of life of the parents and children after use of study medication
Time frame: 3 minutes
contentment and anxiety of the parents
Time frame: 10 minutes
Results and safety
The study was stopped early (reason given: results of interim analysis (not safety relevant)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2018.
- Background: PubMed 23806032Ohlraun 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.
- Derived from this study: PubMed 41433250Weiss C, Hucko A, Muller-Ohlraun S, Marschenz S, Martus P, Schmitz D, Schuelke M. The use of carbogen for interruption of febrile seizures - the randomized controlled CARDIF trial. PLoS One. 2025 Dec 23;20(12):e0324422. doi: 10.1371/journal.pone.0324422. eCollection 2025.
- Homepage of the NeuroCure Clinical Resaerch Center at the Charité BerlinLink provided by the sponsor.
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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.
Markus Schülke-Gerstenfeld principal investigator
Charite - NeuroCure
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 Carbogen in people with Febrile Seizure, run by Charite University, Berlin, Germany at 1 site in Germany.
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 6 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 26 Jan 2018. 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 Germany. 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: results of interim analysis (not safety relevant)). 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?
number of patients which need Diazepam (time frame: 3 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01370044, which also lists 2 linked publications.
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 26 Jan 2018.