Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications

University Hospital, Limoges197 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

197

Conditions

Ventilator-associated Pneumonia Cardiac Arrests With Shockable Rhythm

Interventions

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (16)

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

...and 6 more locations

Outcomes

Primary Outcomes

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

Time frame: 7 days

Secondary Outcomes

Mortality

Time frame: 28 days

Early nosocomial infectious complications

Time frame: 28 days