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

Out-of-hospital Cardiac Arrest Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02899507
• Other study ID #: P3-0331
• Status: Completed
• Phase: Phase 4
• First received: June 30, 2016
• Last updated: September 8, 2016
• Start date: September 2013
• Est. completion date: April 2015

Study information

• Verified date: August 2016
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Health authority: Slovenia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

Drug:
• Amoxicillin-Clavulanic acid
Patients without evidence of tracheobronchial aspiration were randomized to immediate prophylactic Amoxicillin-Clavulanic acid 1,2 gr/8h

Locations

Country	Name	City	State
Slovenia	University Medical Centre Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (7)

Gajic O, Festic E, Afessa B. Infectious complications in survivors of cardiac arrest admitted to the medical intensive care unit. Resuscitation. 2004 Jan;60(1):65-9. — View Citation

Kocjancic ST, Jazbec A, Noc M. Impact of intensified postresuscitation treatment on outcome of comatose survivors of out-of-hospital cardiac arrest according to initial rhythm. Resuscitation. 2014 Oct;85(10):1364-9. doi: 10.1016/j.resuscitation.2014.06.028. Epub 2014 Jul 8. — View Citation

Mongardon N, Perbet S, Lemiale V, Dumas F, Poupet H, Charpentier J, Péne F, Chiche JD, Mira JP, Cariou A. Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era. Crit Care Med. 2011 Jun;39(6):1359-64. doi: 10.1097/CCM.0b013e3182120b56. — View Citation

Perbet S, Mongardon N, Dumas F, Bruel C, Lemiale V, Mourvillier B, Carli P, Varenne O, Mira JP, Wolff M, Cariou A. Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med. 2011 Nov 1;184(9):1048-54. doi: 10.1164/rccm.201102-0331OC. — View Citation

Stub D, Hengel C, Chan W, Jackson D, Sanders K, Dart AM, Hilton A, Pellegrino V, Shaw JA, Duffy SJ, Bernard S, Kaye DM. Usefulness of cooling and coronary catheterization to improve survival in out-of-hospital cardiac arrest. Am J Cardiol. 2011 Feb 15;107(4):522-7. doi: 10.1016/j.amjcard.2010.10.011. Epub 2010 Dec 22. — View Citation

Tømte O, Andersen GØ, Jacobsen D, Drægni T, Auestad B, Sunde K. Strong and weak aspects of an established post-resuscitation treatment protocol-A five-year observational study. Resuscitation. 2011 Sep;82(9):1186-93. doi: 10.1016/j.resuscitation.2011.05.003. Epub 2011 May 14. — View Citation

Woo JH, Lim YS, Yang HJ, Park WB, Cho JS, Kim JJ, Hyun SY, Lee G. Factors associated with pneumonia in post-cardiac arrest patients receiving therapeutic hypothermia. Am J Emerg Med. 2014 Feb;32(2):150-5. doi: 10.1016/j.ajem.2013.10.035. Epub 2013 Oct 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Incidence of positive hemocultures		From the admission until the patient was transferred to the ward. This was always during the ICU stay-one month	No
Secondary	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	No
Secondary	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	No
Secondary	ICU stay		From the admission until the patient was transferred to ward, usually less than one month	No
Secondary	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	No