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Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications (ANTHARTIC)

Primary Purpose

Ventilator-associated Pneumonia, Cardiac Arrests With Shockable Rhythm, Mild Therapeutic Hypothermia

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Amoxicillin - clavulanic acid
Placebo
Sponsored by
University Hospital, Limoges
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ventilator-associated Pneumonia focused on measuring ventilator-associated pneumonia, cardiac arrests with shockable rhythm, Mild therapeutic hypothermia, preventive antibiotics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • CH Angouleme - Service de Réanimation
  • CH Argenteuil - Service de Réanimation
  • CH Brive La Gaillarde - Service de Réanimation
  • CHU Dijon - Serve de Réanimation
  • AP-HP - Hôpital pointcaré - Service de Réanimation
  • CH du MANS
  • CHU de Limoges - Service de réanimation polyvalente
  • CHU Nantes - Service de réanimation
  • CHU Orléans - service de Réanimation
  • AP-HP - Hôpital Lariboisière - Service de Réanimation
  • AP-HP - Hôpital Cochin - Service de Réanimation
  • AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation
  • CH Périgueux
  • CHU Strasbourg - service de Réanimation
  • CHU Tours - Service de Réanimation
  • CH Versailles - service de Réanimation

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Amoxicillin clavulanic acid

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mortality
Mortality
Early nosocomial infectious complications

Full Information

First Posted
July 8, 2014
Last Updated
March 16, 2020
Sponsor
University Hospital, Limoges
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1. Study Identification

Unique Protocol Identification Number
NCT02186951
Brief Title
Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications
Acronym
ANTHARTIC
Official Title
Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 18, 2014 (Actual)
Primary Completion Date
October 27, 2016 (Actual)
Study Completion Date
September 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Limoges

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Multicenter add-on randomized controlled double-blind trial assessing the efficacy of preventive antibiotics amoxicillin-clavulanic acid vs placebo to prevent occurrence of early VAP after out-of-hospital cardiac arrest receiving mild therapeutic hypothermia, in addition to usual VAP prevention measures.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ventilator-associated Pneumonia, Cardiac Arrests With Shockable Rhythm, Mild Therapeutic Hypothermia, Preventive Antibiotics
Keywords
ventilator-associated pneumonia, cardiac arrests with shockable rhythm, Mild therapeutic hypothermia, preventive antibiotics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
197 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amoxicillin clavulanic acid
Arm Type
Experimental
Arm Description
Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin - clavulanic acid
Intervention Description
Amoxicillin-clavulanic acid 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 1g, three times a day during 2 days, started within one hour after randomization and before the beginning of hypothermia.
Primary Outcome Measure Information:
Title
Incidence reduction of early VAP
Description
Incidence reduction of early VAP with short term amoxicillin-clavulanic acid in patients treated with hypothermia after out-of-hospital cardiac arrest
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Mortality
Description
Mortality
Time Frame
28 days
Title
Early nosocomial infectious complications
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno FRANCOIS, MD
Organizational Affiliation
Limoges UH
Official's Role
Principal Investigator
Facility Information:
Facility Name
CH Angouleme - Service de Réanimation
City
Angoulême
State/Province
Saint Michel
ZIP/Postal Code
16470
Country
France
Facility Name
CH Argenteuil - Service de Réanimation
City
Argenteuil
ZIP/Postal Code
95107
Country
France
Facility Name
CH Brive La Gaillarde - Service de Réanimation
City
Brive La Gaillarde
ZIP/Postal Code
19100
Country
France
Facility Name
CHU Dijon - Serve de Réanimation
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
AP-HP - Hôpital pointcaré - Service de Réanimation
City
Garches
ZIP/Postal Code
92380
Country
France
Facility Name
CH du MANS
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Name
CHU de Limoges - Service de réanimation polyvalente
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
CHU Nantes - Service de réanimation
City
Nantes
Country
France
Facility Name
CHU Orléans - service de Réanimation
City
Orleans
ZIP/Postal Code
47067
Country
France
Facility Name
AP-HP - Hôpital Lariboisière - Service de Réanimation
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
AP-HP - Hôpital Cochin - Service de Réanimation
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CH Périgueux
City
Perigueux
ZIP/Postal Code
24019
Country
France
Facility Name
CHU Strasbourg - service de Réanimation
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
CHU Tours - Service de Réanimation
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
CH Versailles - service de Réanimation
City
Versailles
ZIP/Postal Code
78000
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
31693806
Citation
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.
Results Reference
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Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications

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