Clinical trial NCT02152358: PTH - Preemptive Treatment for Herpesviridae
Official title: Efficacy of a Preemptive Treatment by Ganciclovir or by Aciclovir in ICU Patients Requiring Prolonged Mechanical Ventilation and Presenting a Viral Replication (CMV and/or HSV) - Prospective, Randomized, Double-blinded Multicenter Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Viral Pneumonia
Keywords: Cytomegalovirus
Herpes simplex virus
ICU
mechanical ventilation
mortality
ventilator-free days
PCR
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2014-06-02
Enrollment: 317
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to show that a preemptive treatment by ganciclovir (for positive CMV viremia) or aciclovir (for positive HSV oro-pharyngeal PCR) is able to increase the number of ventilator-free days at Day 60.


Eligibility criteria: Inclusion Criteria:

* mechanical ventilation \> 96 hrs and expected duration of mechanical ventilation of at least 2 days
* positive blood CMV PCR (500 IU/ml) OR positive oropharyngeal HSV PCR
* age \> 18 years
* informed consent
* negative pregnancy test

Exclusion Criteria:

* \< 18 years
* Receiving ganciclovir or aciclovir or another antiviral agent active against HSV/CMV
* Had received antiviral agent active against HSV/CMV during the previous month
* Hypersensitivity to aciclovir/ganciclovir
* Pregnancy
* Breast feeding
* Bone marrow failure
* Solid organ recipients
* Bone marrow recipients
* HIV positive patients
* Receiving immunosuppressive agents
* SAPS II \> 75
* Withdrawing/withholding
* Neutropenia (\< 500 mm3)
* Thrombocytopenia (\< 25 G/L)
* ICU readmission

Primary outcomes:
measure: Ventilator-free days at Day 60
timeFrame: 60 days
Secondary outcomes:
measure: Day 60 mortality
timeFrame: 60 days
measure: ICU mortality
timeFrame: 60 days
measure: Hospital mortality
timeFrame: 60 days
measure: Duration of mechanical ventilation in survivors
timeFrame: 60 days
measure: Duration of ICU stay
timeFrame: 60 days
measure: Duration of hospital stay
timeFrame: 60 days
measure: Incidence of ventilator-associated pneumonia
timeFrame: 60 days
measure: Incidence of bacteremia
timeFrame: 60 days
measure: SOFA score
timeFrame: days 3, 5, 7, 14, 21 and 28
measure: Acute renal failure related to aciclovir or its placebo
timeFrame: 60 days
measure: Leucopenia related to ganciclovir or its placebo
timeFrame: 60 days
measure: Time to oropharyngeal negativation of HSV PCR
timeFrame: 30 days
measure: Time to blood negativation of CMV PCR
timeFrame: 30 days
measure: Incidence of herpetic bronchopneumonia
timeFrame: 60 days
measure: Incidence of active CMV infection
timeFrame: 60 days
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique - Hôpitaux de Marseille
Study officials:
affiliation: APHM - AMU
name: Laurent Papazian, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Luyt CE, Forel JM, Hajage D, Jaber S, Cayot-Constantin S, Rimmele T, Coupez E, Lu Q, Diallo MH, Penot-Ragon C, Clavel M, Schwebel C, Timsit JF, Bedos JP, Hauw-Berlemont C, Bourenne J, Mayaux J, Lefrant JY, Mira JP, Combes A, Wolff M, Chastre J, Papazian L; Preemptive Treatment for Herpesviridae Study Group, Reseau Europeen de recherche en Ventilation Artificielle Network. Acyclovir for Mechanically Ventilated Patients With Herpes Simplex Virus Oropharyngeal Reactivation: A Randomized Clinical Trial. JAMA Intern Med. 2020 Feb 1;180(2):263-272. doi: 10.1001/jamainternmed.2019.5713.