Antibiotherapy During Therapeutic Hypothermia to Prevent Infectious Complications

Ventilator-associated Pneumonia Clinical Trial

— ANTHARTIC  

Official title:

Prevention of Early Ventilator-associated Pneumonia With Antibiotic Therapy in Patients Treated With Mild Therapeutic Hypothermia After Cardiac Arrest.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02186951
• Other study ID #: I13018 ANTHARTIC
• Status: Completed
• Phase: Phase 3
• Start date: August 18, 2014
• Est. completion date: September 14, 2017

Study information

• Verified date: March 2020
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: September 14, 2017
• Est. primary completion date: October 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrests With Shockable Rhythm
• Heart Arrest
• Hypothermia
• Mild Therapeutic Hypothermia
• Pneumonia
• Pneumonia, Ventilator-Associated
• Preventive Antibiotics
• Ventilator-associated Pneumonia

Intervention

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

Locations

Country	Name	City	State
France	CH Angouleme - Service de Réanimation	Angoulême	Saint Michel
France	CH Argenteuil - Service de Réanimation	Argenteuil
France	CH Brive La Gaillarde - Service de Réanimation	Brive La Gaillarde
France	CHU Dijon - Serve de Réanimation	Dijon
France	AP-HP - Hôpital pointcaré - Service de Réanimation	Garches
France	CH du MANS	Le Mans
France	CHU de Limoges - Service de réanimation polyvalente	Limoges
France	CHU Nantes - Service de réanimation	Nantes
France	CHU Orléans - service de Réanimation	Orleans
France	AP-HP - Hôpital Cochin - Service de Réanimation	Paris
France	AP-HP - Hôpital Européen Georges Pompidou - Service de Réanimation	Paris
France	AP-HP - Hôpital Lariboisière - Service de Réanimation	Paris
France	CH Périgueux	Perigueux
France	CHU Strasbourg - service de Réanimation	Strasbourg
France	CHU Tours - Service de Réanimation	Tours
France	CH Versailles - service de Réanimation	Versailles

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

References & Publications (1)

François B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefève 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-TRIGG — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mortality	Mortality	28 days
Secondary	Early nosocomial infectious complications		28 days