Prophylactic Antibiotics in Comatose Survivors of Out-of-hospital Cardiac Arrest

Study Overview
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Brief Summary
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The purpose of this study is to determine whether there is potential benefits of prophylactic antibiotic treatment in comatose survivors of out-of-hospital cardiac arrest (OHCA) treated in intensive care unit with therapeutic hypothermia.

Detailed Description
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Postresuscitation management of comatose survivors of out-of-hospital cardiac arrest (OHCA) significantly improved and bundle of care including therapeutic hypothermia, immediate coronary angiography, percutaneous coronary intervention (PCI) and contemporary intensive care nowadays leads to survival with good neurological recovery. Benefit of prophylactic antibiotics, which may suppress development of postresuscitation infection and especially early onset pneumonia and thereby decrease the severity of postresuscitation systemic inflammatory response, is controversial. Because of these uncertainties, the investigators performed a single-center randomized clinical trial comparing prophylactic versus clinically-driven administration of antibiotics in comatose survivors of OHCA. The investigators hypothesized that prophylactic antibiotics may decrease the severity of postresuscitation systemic inflammatory response by reducing the incidence of postresuscitation infection and especially pneumonia which was further addressed by repeat microbiological sampling.

Official Title
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Prophylactic Versus Clinically-driven Antibiotics in Comatose Survivors of Out-of-hospital Cardiac Arrest

Conditions
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Out-of-hospital Cardiac Arrest

Intervention / Treatment
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* Drug: Amoxicillin-Clavulanic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male over 18 years old Comatose survivors of out-of-hospital cardiac arrest treated in intensive care unit with therapeutic hypothermia Exclusion Criteria: Suspected or confirmed pregnancy Allergy to amoxicillin-clavulanic acid Tracheobronchial aspiration Antibiotic therapy before cardiac arrest Need of antibiotics due to other causes Candidates for immediate veno-arterial extracorporeal membrane oxygenation (VA ECMO) Patients in whom no active treatment was decided on admission

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylactic antibiotic<br>Amoxicillin-Clavulanic acid 1.2g every 8h | Drug: Amoxicillin-Clavulanic acid<br>* Patients without evidence of tracheobronchial aspiration were randomized to immediate prophylactic Amoxicillin-Clavulanic acid 1,2 gr/8h<br>* Other names: Amoksiklav, Augmentin;|
| No Intervention: Clinically-driven antibiotics<br>Administration of antibiotics in clinically-driven group was at the discretion of attending intensivist. Selection of antibiotic in clinically-driven group was empirical or based on the results of bacterial cultures if already available. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Value of C-reactive protein (CRP) at day three | Expressed in milligram/litre (normal <5 mg/L) | Three days after admission to Intensive care unit (ICU) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of systemic inflammatory response estimated by peak white blood cell count (WBC) | Expressed in number of white blood cells x 109 per litre (L) | First measurement at admission in hospital and afterwards in 24 hours intervals during stay in the intensive care unite (ICU) but not longer then first seven days | 
| Severity of systemic inflammatory response estimated by peak value of procalcitonin (PCT) | Expressed in microgram/litre (normal <0.5 microgram/L) | First measurement at admission in hospital and afterwards in 24 hours intervals during stay in the intensive care unite (ICU) but not longer then first seven days | 
| Severity of systemic inflammatory response estimated by peak value of neutrophil Cluster of differentiation 64 (CD 64) | Neutrophil CD 64 expression was used as an index of sepsis with >1.2 indicating greater likelihood of sepsis | First measurement at admission in hospital and afterwards in 24 hours intervals in the first three days | 
| Appearance of pneumonia on chest X ray |  | Chest X ray was taken on admission and afterwards on daily basis during the stay in the intensive care unite but not longer than first week | 
| Incidence of positive blind mini bronchoalveolar lavage (Mini-BAL) on day 3 |  | Mini-BAL was performed on the third day after the sudden cardiac arrest | 
| Incidence of positive hemocultures |  | From the admission until the patient was transferred to the ward. This was always during the ICU stay-one month | 
| Duration of tracheal intubation | Duration of intubation was expressed as days of intubation started with admission until the extubation. Because this is being done in intensive care unite, the time frame is duration of ICU stay | From the day of admission until the extubation. This was always during the ICU stay- one month | 
| Duration of mechanical ventilation | Duration of mechanical ventilation was expressed as days the patient needed the mechanical support for breathing regardless of mode of support | From the admission until spontaneous breathing . This was during ICU stay-one month | 
| ICU stay |  | From the admission until the patient was transferred to ward, usually less than one month | 
| Survival with good neurological outcome | Good neurological outcome was characterised using cerebral performance category (CPC) with 1-2 indicating good neurological recovery. | Up to six months after the event | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Out-of-hospital cardiac arrest, Prophylactic antibiotics