Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications (ANTHARTIC)

University of Limoges (UL)

Status and phase: Completed; Phase 3

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

Treatments: Drug: Amoxicillin - clavulanic acid; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02186951

I13018 ANTHARTIC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 197 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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197 participants in 2 patient groups, including a placebo group

Amoxicillin clavulanic acid

Experimental group

Description:

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

Treatment:

Drug: Amoxicillin - clavulanic acid

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo