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

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ClinicalTrials.gov Identifier: NCT02899507
Recruitment Status : Completed
First Posted : September 14, 2016
Last Update Posted : September 14, 2016
Sponsor:
Information provided by (Responsible Party):
Marko Noc, University Medical Centre Ljubljana

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Out-of-hospital Cardiac Arrest Drug: Amoxicillin-Clavulanic acid Phase 4

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prophylactic Versus Clinically-driven Antibiotics in Comatose Survivors of Out-of-hospital Cardiac Arrest
Study Start Date : September 2013
Actual Primary Completion Date : March 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Prophylactic antibiotic
Amoxicillin-Clavulanic acid 1.2g every 8h
Drug: Amoxicillin-Clavulanic acid
Patients without evidence of tracheobronchial aspiration were randomized to immediate prophylactic Amoxicillin-Clavulanic acid 1,2 gr/8h
Other Name: Amoksiklav, Augmentin

No Intervention: Clinically-driven antibiotics
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.



Primary Outcome Measures :
  1. Value of C-reactive protein (CRP) at day three [ Time Frame: Three days after admission to Intensive care unit (ICU) ]
    Expressed in milligram/litre (normal <5 mg/L)


Secondary Outcome Measures :
  1. Severity of systemic inflammatory response estimated by peak white blood cell count (WBC) [ Time Frame: 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 ]
    Expressed in number of white blood cells x 109 per litre (L)

  2. Severity of systemic inflammatory response estimated by peak value of procalcitonin (PCT) [ Time Frame: 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 ]
    Expressed in microgram/litre (normal <0.5 microgram/L)

  3. Severity of systemic inflammatory response estimated by peak value of neutrophil Cluster of differentiation 64 (CD 64) [ Time Frame: First measurement at admission in hospital and afterwards in 24 hours intervals in the first three days ]
    Neutrophil CD 64 expression was used as an index of sepsis with >1.2 indicating greater likelihood of sepsis

  4. Appearance of pneumonia on chest X ray [ Time Frame: 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 ]
  5. Incidence of positive blind mini bronchoalveolar lavage (Mini-BAL) on day 3 [ Time Frame: Mini-BAL was performed on the third day after the sudden cardiac arrest ]
  6. Incidence of positive hemocultures [ Time Frame: From the admission until the patient was transferred to the ward. This was always during the ICU stay-one month ]
  7. Duration of tracheal intubation [ Time Frame: From the day of admission until the extubation. This was always during the ICU stay- one month ]
    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

  8. Duration of mechanical ventilation [ Time Frame: From the admission until spontaneous breathing . This was during ICU stay-one month ]
    Duration of mechanical ventilation was expressed as days the patient needed the mechanical support for breathing regardless of mode of support

  9. ICU stay [ Time Frame: From the admission until the patient was transferred to ward, usually less than one month ]
  10. Survival with good neurological outcome [ Time Frame: Up to six months after the event ]
    Good neurological outcome was characterised using cerebral performance category (CPC) with 1-2 indicating good neurological recovery.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02899507


Locations
Slovenia
University Medical Centre Ljubljana
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
University Medical Centre Ljubljana
Investigators
Principal Investigator: Marko Noč, MD, PhD University Medical Centre Ljubljana

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Marko Noc, MD, PhD, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT02899507     History of Changes
Other Study ID Numbers: P3-0331
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: September 14, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Marko Noc, University Medical Centre Ljubljana:
Out-of-hospital cardiac arrest
Prophylactic antibiotics

Additional relevant MeSH terms:
Heart Arrest
Out-of-Hospital Cardiac Arrest
Heart Diseases
Cardiovascular Diseases
Anti-Bacterial Agents
Amoxicillin
Clavulanic Acids
Clavulanic Acid
Amoxicillin-Potassium Clavulanate Combination
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
beta-Lactamase Inhibitors