NCT02186951

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
197

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Aug 2014

Typical duration for phase_3

Geographic Reach
1 country

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 8, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 10, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

August 18, 2014

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 27, 2016

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 14, 2017

Completed
Last Updated

March 18, 2020

Status Verified

March 1, 2020

Enrollment Period

2.2 years

First QC Date

July 8, 2014

Last Update Submit

March 16, 2020

Conditions

Ventilator-associated PneumoniaCardiac Arrests With Shockable RhythmMild Therapeutic HypothermiaPreventive Antibiotics

Keywords

ventilator-associated pneumoniacardiac arrests with shockable rhythmMild therapeutic hypothermiapreventive antibiotics

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Mortality

    28 days

  • Early nosocomial infectious complications

    28 days

Study Arms (2)

Amoxicillin clavulanic acid

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Drug: Placebo

Interventions

Amoxicillin - clavulanic acidDRUG

Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Amoxicillin clavulanic acid
PlaceboDRUG

Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

CH Angouleme - Service de Réanimation

Angoulême, Saint Michel, 16470, France

Location

CH Argenteuil - Service de Réanimation

Argenteuil, 95107, France

Location

CH Brive La Gaillarde - Service de Réanimation

Brive-la-Gaillarde, 19100, France

Location

CHU Dijon - Serve de Réanimation

Dijon, 21079, France

Location

AP-HP - Hôpital pointcaré - Service de Réanimation

Garches, 92380, France

Location

CH du MANS

Le Mans, 72000, France

Location

CHU de Limoges - Service de réanimation polyvalente

Limoges, 87042, France

Location

CHU Nantes - Service de réanimation

Nantes, France

Location

CHU Orléans - service de Réanimation

Orléans, 47067, France

Location

AP-HP - Hôpital Lariboisière - Service de Réanimation

Paris, 75010, France

Location

AP-HP - Hôpital Cochin - Service de Réanimation

Paris, 75014, France

Location

AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation

Paris, 75015, France

Location

CH Périgueux

Périgueux, 24019, France

Location

CHU Strasbourg - service de Réanimation

Strasbourg, 67000, France

Location

CHU Tours - Service de Réanimation

Tours, 37044, France

Location

CH Versailles - service de Réanimation

Versailles, 78000, France

Location

Related Publications (1)

  • Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.

    PMID: 31693806RESULT

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Healthcare-Associated PneumoniaCross InfectionInfectionsPneumoniaRespiratory Tract InfectionsLung DiseasesRespiratory Tract DiseasesIatrogenic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clavulanic AcidClavulanic Acidsbeta-LactamsLactamsAmidesOrganic ChemicalsAmoxicillinAmpicillinPenicillin GPenicillinsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Bruno FRANCOIS, MD

    Limoges UH

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2014

First Posted

July 10, 2014

Study Start

August 18, 2014

Primary Completion

October 27, 2016

Study Completion

September 14, 2017

Last Updated

March 18, 2020

Record last verified: 2020-03

Locations

FR(16)