Out-of-hospital Cardiac ArrestPhase 4NCT02899507

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

A Phase 4 study testing Amoxicillin-Clavulanic acid in people with Out-of-hospital Cardiac Arrest, run by University Medical Centre Ljubljana at 1 site in Slovenia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Out-of-hospital Cardiac Arrest
What is being tested?: Amoxicillin-Clavulanic acid
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 1 siteSlovenia
Study dates: Sep 2013to Apr 2015
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Female and male over 18 years old
Comatose survivors of out-of-hospital cardiac arrest treated in intensive care unit with therapeutic hypothermia

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Slovenia1 site

University Medical Centre Ljubljana
Ljubljana, 1000

Other trials in Slovenia

About this study

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

Read the 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.

Conditions: Out-of-hospital Cardiac Arrest
Being tested: Amoxicillin-Clavulanic acid
Keywords: Out-of-hospital cardiac arrest, Prophylactic antibiotics
Medical subject headings: Out-of-Hospital Cardiac Arrest

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Amoxicillin-Clavulanic acidDrug
Also called Amoksiklav, Augmentin
Patients without evidence of tracheobronchial aspiration were randomized to immediate prophylactic Amoxicillin-Clavulanic acid 1,2 gr/8h

Study groups in NCT02899507
Study group	Role	What they receive
Prophylactic antibiotic	Experimental	Amoxicillin-Clavulanic acid 1.2g every 8h Receives: Drug: Amoxicillin-Clavulanic acid
Clinically-driven antibiotics	No intervention	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 being measured

The primary outcome is the main question the study is designed to answer.

Value of C-reactive protein (CRP) at day three
Expressed in milligram/litre (normal <5 mg/L)
Measured: Three days after admission to Intensive care unit (ICU)

Secondary outcomes (10)

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)
Measured: 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)
Measured: 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
Measured: First measurement at admission in hospital and afterwards in 24 hours intervals in the first three days
Appearance of pneumonia on chest X ray
Measured: 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
Measured: Mini-BAL was performed on the third day after the sudden cardiac arrest
Incidence of positive hemocultures
Measured: 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
Measured: 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
Measured: From the admission until spontaneous breathing . This was during ICU stay-one month
ICU stay
Measured: 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.
Measured: Up to six months after the event

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2013Apr 2015

First posted14 Sep 2016 (estimated)
Study startSep 2013
Primary completionMar 2015
Study completionApr 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Out-of-hospital Cardiac ArrestStudies of the same condition, open and under way.
More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02899507
Sponsor's protocol ID: P3-0331
Status last verified: Aug 2016
First submitted: 30 Jun 2016
Last updated: 14 Sep 2016
Results posted: No
Data monitoring committee: No
Individual data sharing: No

Publications

Tomte O, Andersen GO, Jacobsen D, Draegni 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.
PubMed 21636202
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.
PubMed 21184989
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.
PubMed 25010782
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.
PubMed 21816940
Mongardon N, Perbet S, Lemiale V, Dumas F, Poupet H, Charpentier J, Pene 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.
PubMed 21336107
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. doi: 10.1016/j.resuscitation.2003.08.005.
PubMed 14987786
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.
PubMed 24268585
Ribaric SF, Turel M, Knafelj R, Gorjup V, Stanic R, Gradisek P, Cerovic O, Mirkovic T, Noc M. Prophylactic versus clinically-driven antibiotics in comatose survivors of out-of-hospital cardiac arrest-A randomized pilot study. Resuscitation. 2017 Feb;111:103-109. doi: 10.1016/j.resuscitation.2016.11.025. Epub 2016 Dec 14.
PubMed 27987397

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
CAROTID DOPPLER AND CEREBRAL OXIMERY IN POST CARDIAC ARREST ICU PATIENTS
Cardiac Arrest (CA), Carotid Doppler
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The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
Not yet recruiting
Compression-Only Versus Standard Basic Life Support Training in Nursing Students
Cardiopulmonary Resuscitation, Out-of-Hospital Cardiac Arrest
Not yet recruiting
Execution of Prehospital Transesophageal Echocardiography During Cardiopulmonary Resuscitation in Patients With Out-of-hospital Cardiac Arrest
Out-of-hospital Cardiac Arrest (OHCA)
Active, not recruiting
The REVIVE-PEEP Trial: Positive End-expiratory Pressure Versus Sham Valve/Zero End-expiratory Pressure in Cardiopulmonary Resuscitation During Manual Ventilation to Improve Neurological Outcomes at Discharge in Adult Patients Suffering an Out-of-hospital Cardiac Arrest
Cardiac Arrest, Out-Of-Hospital

All Out-of-hospital Cardiac Arrest trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prophylactic Versus Clinically-driven Antibiotics in Comatose Survivors of Out-of-hospital Cardiac Arrest
ClinicalTrials.gov ID: NCT02899507
Acronym / sponsor ID: P3-0331
Conditions: Out-of-hospital Cardiac Arrest
Keywords: Out-of-hospital cardiac arrest, Prophylactic antibiotics
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: University Medical Centre LjubljanaUniversity, hospital or other
Study start: Sep 2013
Primary completion: Mar 2015 (actual)
Study completion: Apr 2015 (actual)
First posted: 14 Sep 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Prophylactic antibiotic	Experimental	Drug: Amoxicillin-Clavulanic acidAmoxicillin-Clavulanic acid 1.2g every 8h
Clinically-driven antibiotics	No intervention	–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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Female and male over 18 years old
Comatose survivors of out-of-hospital cardiac arrest treated in intensive care unit with therapeutic hypothermia

Key exclusion criteria (7 listed)

Suspected or confirmed pregnancy
Allergy to amoxicillin-clavulanic acid
Tracheobronchial aspiration
Antibiotic therapy before cardiac arrest
Need of antibiotics due to other causes

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Amoxicillin-Clavulanic acidAlso: Amoksiklav, AugmentinPatients without evidence of tracheobronchial aspiration were randomized to immediate prophylactic Amoxicillin-Clavulanic acid 1,2 gr/8h	Drug	Prophylactic antibiotic

Primary outcome

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)

10 secondary outcomes

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
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
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
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
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
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
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 mechanical ventilation
Time frame: From the admission until spontaneous breathing . This was during ICU stay-one month
ICU stay
Time frame: From the admission until the patient was transferred to ward, usually less than one month
Survival with good neurological outcome
Time frame: Up to six months after the event

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2016.
Background: PubMed 21636202Tomte O, Andersen GO, Jacobsen D, Draegni 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.
Background: PubMed 21184989Stub 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.
Background: PubMed 25010782Kocjancic 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.
Background: PubMed 21816940Perbet 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.
Background: PubMed 21336107Mongardon N, Perbet S, Lemiale V, Dumas F, Poupet H, Charpentier J, Pene 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.
Background: PubMed 14987786Gajic 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. doi: 10.1016/j.resuscitation.2003.08.005.
Background: PubMed 24268585Woo 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.
Derived from this study: PubMed 27987397Ribaric SF, Turel M, Knafelj R, Gorjup V, Stanic R, Gradisek P, Cerovic O, Mirkovic T, Noc M. Prophylactic versus clinically-driven antibiotics in comatose survivors of out-of-hospital cardiac arrest-A randomized pilot study. Resuscitation. 2017 Feb;111:103-109. doi: 10.1016/j.resuscitation.2016.11.025. Epub 2016 Dec 14.
Individual participant dataSharing planned: No

Related trials for Out-of-hospital Cardiac Arrest

Not yet recruitingObservational study
CAROTID DOPPLER AND CEREBRAL OXIMERY IN POST CARDIAC ARREST ICU PATIENTS
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Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
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Execution of Prehospital Transesophageal Echocardiography During Cardiopulmonary Resuscitation in Patients With Out-of-hospital Cardiac Arrest
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The REVIVE-PEEP Trial: Positive End-expiratory Pressure Versus Sham Valve/Zero End-expiratory Pressure in Cardiopulmonary Resuscitation During Manual Ventilation to Improve Neurological Outcomes at Discharge in Adult Patients Suffering an Out-of-hospital Cardiac Arrest
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marko Noč, MD, PhD principal investigator

University Medical Centre Ljubljana

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Amoxicillin-Clavulanic acid in people with Out-of-hospital Cardiac Arrest, run by University Medical Centre Ljubljana at 1 site in Slovenia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Value of C-reactive protein (CRP) at day three (time frame: Three days after admission to Intensive care unit (ICU)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02899507, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2016.