Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications

Phase 3

Completed

• Conditions: Cardiac Arrests With Shockable Rhythm; Mild Therapeutic Hypothermia; Preventive Antibiotics; Ventilator-associated Pneumonia
• Interventions: Drug: Amoxicillin - clavulanic acid; Drug: Placebo

• Registration Number: NCT02186951
• Lead Sponsor: University Hospital, Limoges

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.

Study Timeline

• Study First Submitted: 2014-07-08
• Study First Submitted QC: 2014-07-09
• Study First Posted: 2014-07-10
• Study Start: 2014-08-18
• Primary Completion: 2016-10-27
• Study Completion: 2017-09-14
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-16
• Last Update Posted: 2020-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 197

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Incidence reduction of early VAP	7 days	Incidence reduction of early VAP with short term amoxicillin-clavulanic acid in patients treated with hypothermia after out-of-hospital cardiac arrest

Secondary Outcome Measures

Name	Time	Method
Mortality	28 days	Mortality
Early nosocomial infectious complications	28 days

Trial Locations

Locations (16)

CHU Strasbourg - service de Réanimation; 🇫🇷 Strasbourg, France

CHU Tours - Service de Réanimation; 🇫🇷 Tours, France

CH Versailles - service de Réanimation; 🇫🇷 Versailles, France

CH Angouleme - Service de Réanimation; 🇫🇷 Angoulême, Saint Michel, France

CH Brive La Gaillarde - Service de Réanimation; 🇫🇷 Brive La Gaillarde, France

CH Périgueux; 🇫🇷 Perigueux, France

AP-HP - Hôpital pointcaré - Service de Réanimation; 🇫🇷 Garches, France

CH Argenteuil - Service de Réanimation; 🇫🇷 Argenteuil, France

CHU Dijon - Serve de Réanimation; 🇫🇷 Dijon, 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; 🇫🇷 Orleans, France

AP-HP - Hôpital Cochin - Service de Réanimation; 🇫🇷 Paris, France

AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation; 🇫🇷 Paris, France

AP-HP - Hôpital Lariboisière - Service de Réanimation; 🇫🇷 Paris, France