Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.

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

Intervention / Treatment
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* Drug: Amoxicillin - clavulanic acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amoxicillin clavulanic acid<br>Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. | Drug: Amoxicillin - clavulanic acid<br>* Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.<br>|
| Placebo Comparator: Placebo<br>Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia. | Drug: Placebo<br>* Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality | 28 days | 
| Early nosocomial infectious complications |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ventilator-associated pneumonia, cardiac arrests with shockable rhythm, Mild therapeutic hypothermia, preventive antibiotics