Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications

NCT ID: NCT02186951

Last Updated: 2020-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 197 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-18
• Study Completion Date: 2017-09-14

Brief 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 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.

Conditions

Ventilator-associated Pneumonia; Cardiac Arrests With Shockable Rhythm; Mild Therapeutic Hypothermia; Preventive Antibiotics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Amoxicillin clavulanic acid

Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Group Type: EXPERIMENTAL

Amoxicillin - clavulanic acid

Intervention Type: DRUG

Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Placebo

Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Interventions

Amoxicillin - clavulanic acid

Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Intervention Type: DRUG

Placebo

Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Limoges

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno FRANCOIS, MD

Role: PRINCIPAL_INVESTIGATOR

Limoges UH

Locations

CH Angouleme - Service de Réanimation

Angoulême, Saint Michel, France

CH Argenteuil - Service de Réanimation

Argenteuil, , France

CH Brive La Gaillarde - Service de Réanimation

Brive-la-Gaillarde, , France

CHU Dijon - Serve de Réanimation

Dijon, , France

AP-HP - Hôpital pointcaré - Service de Réanimation

Garches, , France

CH du MANS

Le Mans, , France

CHU de Limoges - Service de réanimation polyvalente

Limoges, , France

CHU Nantes - Service de réanimation

Nantes, , France

CHU Orléans - service de Réanimation

Orléans, , France

AP-HP - Hôpital Lariboisière - Service de Réanimation

Paris, , France

AP-HP - Hôpital Cochin - Service de Réanimation

Paris, , France

AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation

Paris, , France

CH Périgueux

Périgueux, , France

CHU Strasbourg - service de Réanimation

Strasbourg, , France

CHU Tours - Service de Réanimation

Tours, , France

CH Versailles - service de Réanimation

Versailles, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 31693806 (View on PubMed)

Other Identifiers

I13018 ANTHARTIC

Identifier Type: -

Identifier Source: org_study_id