Clinical trial NCT02186951: Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications
Official title: Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2014-07-10
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence reduction of early VAP
timeFrame: 7 days
Secondary outcomes:
measure: Mortality
timeFrame: 28 days
measure: Early nosocomial infectious complications
timeFrame: 28 days
Other outcomes:
Locations:
city: Angoulême
country: France
facility: CH Angouleme - Service de Réanimation
state: Saint Michel
city: Argenteuil
country: France
facility: CH Argenteuil - Service de Réanimation
city: Brive La Gaillarde
country: France
facility: CH Brive La Gaillarde - Service de Réanimation
city: Dijon
country: France
facility: CHU Dijon - Serve de Réanimation
city: Garches
country: France
facility: AP-HP - Hôpital pointcaré - Service de Réanimation
city: Le Mans
country: France
facility: CH du MANS
city: Limoges
country: France
facility: CHU de Limoges - Service de réanimation polyvalente
city: Nantes
country: France
facility: CHU Nantes - Service de réanimation
city: Orleans
country: France
facility: CHU Orléans - service de Réanimation
city: Paris
country: France
facility: AP-HP - Hôpital Lariboisière - Service de Réanimation
city: Paris
country: France
facility: AP-HP - Hôpital Cochin - Service de Réanimation
city: Paris
country: France
facility: AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation
city: Perigueux
country: France
facility: CH Périgueux
city: Strasbourg
country: France
facility: CHU Strasbourg - service de Réanimation
city: Tours
country: France
facility: CHU Tours - Service de Réanimation
city: Versailles
country: France
facility: CH Versailles - service de Réanimation
Study officials:
affiliation: Limoges UH
name: Bruno FRANCOIS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.