Ventilator-associated PneumoniaPhase 3ANTHARTICNCT02186951
Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications
A Phase 3 study testing Amoxicillin - clavulanic acid in people with Ventilator-associated Pneumonia and Cardiac Arrests With Shockable Rhythm, run by University Hospital, Limoges at 16 sites in France.
Trial summary
Mild therapeutic hypothermia is currently recommended in management of cardiac arrests with shockable rhythm. In mechanically ventilated patients who were resuscitated after out-of-hospital cardiac arrests, mild therapeutic hypothermia side effects are conductive for infectious complications and especially for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator-associated Pneumonia, Cardiac Arrests With Shockable Rhythm, Mild Therapeutic Hypothermia
- What is being tested?
- Amoxicillin - clavulanic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 197 participants
- Where
- 16 sitesFrance
- Study dates
- 18 Aug 2014to 14 Sep 2017
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Older than 18 years-old, intubated and mechanically ventilated after out-of-hospital resuscitated cardiac arrest secondary to shockable rhythm
- Hospitalized in an ICU
- Mild therapeutic hypothermia procedure (32° to 35°C) scheduled (24 to 36 hours)
- Delay from ROSC to randomisation < 6 hours
- Consent from family members or emergency consent
Who cannot join
- Pregnancy
- Out-of-hospital cardiac arrest secondary to non shockable rhythm and In-hospital cardiac arrest
- Need for cardiac support by cardiopulmonary bypass
- Ongoing antibiotic therapy or during the week before
- Ongoing or concomitant pneumonia
- Known chronic colonization with MRB
Show all 14Show fewer
- Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients.
- History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).
- History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid, according to the latest version of the SmPC.
- Previous lung disease
- Predictable decision of early care limitation
- Patient under guardianship or curatorship
- Moribund patient
- Participation to another trial within 30 days
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
France16 sites
CH Angouleme - Service de Réanimation
Angoulême, Saint Michel, 16470
CH Argenteuil - Service de Réanimation
Argenteuil, 95107
CH Brive La Gaillarde - Service de Réanimation
Brive-la-Gaillarde, 19100
CHU Dijon - Serve de Réanimation
Dijon, 21079
AP-HP - Hôpital pointcaré - Service de Réanimation
Garches, 92380
CH du MANS
Le Mans, 72000
CHU de Limoges - Service de réanimation polyvalente
Limoges, 87042
CHU Nantes - Service de réanimation
Nantes
CHU Orléans - service de Réanimation
Orléans, 47067
AP-HP - Hôpital Lariboisière - Service de Réanimation
Paris, 75010
AP-HP - Hôpital Cochin - Service de Réanimation
Paris, 75014
AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation
Paris, 75015
CH Périgueux
Périgueux, 24019
CHU Strasbourg - service de Réanimation
Strasbourg, 67000
CHU Tours - Service de Réanimation
Tours, 37044
CH Versailles - service de Réanimation
Versailles, 78000
About this study
Official title: Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.
Mild therapeutic hypothermia is currently recommended in management of cardiac arrests with shockable rhythm. In mechanically ventilated patients who were resuscitated after out-of-hospital cardiac arrests, mild therapeutic hypothermia side effects are conductive for infectious complications and especially for ventilator-associated pneumonia (VAP).
Despite high incidence of VAP and other infectious complications, it is not currently recommended to use antibiotic prophylaxis on the responsible germs. Yet VAP incidence could be decreased if an antibiotic therapy was systematically given to patient treated with mild therapeutic hypothermia after a cardiac arrest. Several retrospective studies showed less infectious complications but also decreased morbidity and mortality related to these complications when antibiotic therapy was given early to patients treated with therapeutic hypothermia after cardiac arrest.
Read the detailed description
Multicenter add-on randomized controlled double-blind trial assessing the efficacy of preventive antibiotics amoxicillin-clavulanic acid vs placebo to prevent occurrence of early VAP after out-of-hospital cardiac arrest receiving mild therapeutic hypothermia, in addition to usual VAP prevention measures.
- Conditions
- Ventilator-associated Pneumonia, Cardiac Arrests With Shockable Rhythm, Mild Therapeutic Hypothermia, Preventive Antibiotics
- Being tested
- Amoxicillin - clavulanic acid, Placebo
- Keywords
- ventilator-associated pneumonia, cardiac arrests with shockable rhythm, Mild therapeutic hypothermia, preventive antibiotics
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amoxicillin - clavulanic acidDrug
Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
PlaceboDrug
Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
| Study group | Role | What they receive |
|---|---|---|
| Amoxicillin clavulanic acid | Experimental | Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. Receives: Drug: Amoxicillin - clavulanic acid |
| Placebo | Placebo comparator | Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence reduction of early VAP
Incidence reduction of early VAP with short term amoxicillin-clavulanic acid in patients treated with hypothermia after out-of-hospital cardiac arrest
Measured: 7 days
Secondary outcomes (2)
Mortality
Mortality
Measured: 28 days
Early nosocomial infectious complications
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2014 (estimated)
- Study start18 Aug 2014
- Primary completion27 Oct 2016
- Study completion14 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ventilator-associated PneumoniaStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruno FRANCOIS, MD, Principal investigator, Limoges UH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02186951
- Sponsor's protocol ID
- I13018 ANTHARTIC
- Acronym
- ANTHARTIC
- Status last verified
- Mar 2020
- First submitted
- 8 Jul 2014
- Last updated
- 18 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.
PubMed 31693806
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.
- ClinicalTrials.gov ID
- NCT02186951
- Acronym / sponsor ID
- ANTHARTIC / I13018 ANTHARTIC
- Conditions
- Ventilator-associated Pneumonia, Cardiac Arrests With Shockable Rhythm, Mild Therapeutic Hypothermia, Preventive Antibiotics
- Keywords
- ventilator-associated pneumonia, cardiac arrests with shockable rhythm, Mild therapeutic hypothermia, preventive antibiotics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- 18 Aug 2014 (actual)
- Primary completion
- 27 Oct 2016 (actual)
- Study completion
- 14 Sep 2017 (actual)
- First posted
- 10 Jul 2014 (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.
Mild therapeutic hypothermia is currently recommended in management of cardiac arrests with shockable rhythm. In mechanically ventilated patients who were resuscitated after out-of-hospital cardiac arrests, mild therapeutic hypothermia side effects are conductive for infectious complications and especially for ventilator-associated pneumonia (VAP).
Despite high incidence of VAP and other infectious complications, it is not currently recommended to use antibiotic prophylaxis on the responsible germs. Yet VAP incidence could be decreased if an antibiotic therapy was systematically given to patient treated with mild therapeutic hypothermia after a cardiac arrest. Several retrospective studies showed less infectious complications but also decreased morbidity and mortality related to these complications when antibiotic therapy was given early to patients treated with therapeutic hypothermia after cardiac arrest.
Detailed description
Multicenter add-on randomized controlled double-blind trial assessing the efficacy of preventive antibiotics amoxicillin-clavulanic acid vs placebo to prevent occurrence of early VAP after out-of-hospital cardiac arrest receiving mild therapeutic hypothermia, in addition to usual VAP prevention measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amoxicillin clavulanic acid | Experimental | Drug: Amoxicillin - clavulanic acidAmoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Older than 18 years-old, intubated and mechanically ventilated after out-of-hospital resuscitated cardiac arrest secondary to shockable rhythm
- Hospitalized in an ICU
- Mild therapeutic hypothermia procedure (32° to 35°C) scheduled (24 to 36 hours)
- Delay from ROSC to randomisation < 6 hours
- Consent from family members or emergency consent
Key exclusion criteria (14 listed)
- Pregnancy
- Out-of-hospital cardiac arrest secondary to non shockable rhythm and In-hospital cardiac arrest
- Need for cardiac support by cardiopulmonary bypass
- Ongoing antibiotic therapy or during the week before
- Ongoing or concomitant pneumonia
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 |
|---|---|---|
| Amoxicillin - clavulanic acidAmoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. | Drug | Amoxicillin clavulanic acid |
| PlaceboPlacebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. | Drug | Placebo |
Primary outcome
Incidence reduction of early VAP
Time frame: 7 days
Incidence reduction of early VAP with short term amoxicillin-clavulanic acid in patients treated with hypothermia after out-of-hospital cardiac arrest
2 secondary outcomes
Mortality
Time frame: 28 days
Early nosocomial infectious complications
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2020.
- Results publication: PubMed 31693806Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.
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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.
Bruno FRANCOIS, MD principal investigator
Limoges UH
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Amoxicillin - clavulanic acid in people with Ventilator-associated Pneumonia and Cardiac Arrests With Shockable Rhythm, run by University Hospital, Limoges at 16 sites in France.
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 5 inclusion and 14 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: finished, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in France. 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 phase mean?
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence reduction of early VAP (time frame: 7 days). 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 NCT02186951, which also lists 1 linked publication.
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 18 Mar 2020.