PTH - Preemptive Treatment for Herpesviridae (PTH)

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

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.

Study Overview

• Status: Completed
• Conditions: Viral Pneumonia
• Intervention / Treatment: Drug: Placebo; Drug: Ganciclovir; Drug: Aciclovir

• Study Type: Interventional
• Enrollment (Actual): 317
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13015
    • Assistance Publique - Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ganciclovir; Patients with a positive CMV PCR	Drug: Ganciclovir; intravenous 10 mg/kg/d for 14 days
Placebo Comparator: Ganciclovir placebo; Patients with a positive CMV PCR	Drug: Placebo
Active Comparator: Aciclovir; Patients with a PCR positive for HSV	Drug: Aciclovir; Intravenous 15 mg/kg/d during 14 days
Placebo Comparator: Aciclovir placebo; Patients with a positive PCR for HSV	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ventilator-free days at Day 60	60 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Day 60 mortality	60 days
ICU mortality	60 days
Hospital mortality	60 days
Duration of mechanical ventilation in survivors	60 days
Duration of ICU stay	60 days
Duration of hospital stay	60 days
Incidence of ventilator-associated pneumonia	60 days
Incidence of bacteremia	60 days
SOFA score	days 3, 5, 7, 14, 21 and 28
Acute renal failure related to aciclovir or its placebo	60 days
Leucopenia related to ganciclovir or its placebo	60 days
Time to oropharyngeal negativation of HSV PCR	30 days
Time to blood negativation of CMV PCR	30 days
Incidence of herpetic bronchopneumonia	60 days
Incidence of active CMV infection	60 days

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Laurent Papazian, MD, PhD, APHM - AMU

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2014
• Primary Completion (Actual): April 21, 2018
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: March 26, 2014
• First Submitted That Met QC Criteria: May 28, 2014
• First Posted (Estimate): June 2, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: mechanical ventilation; ICU; PCR; mortality; Cytomegalovirus; Herpes simplex virus; ventilator-free days
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Pneumonia, Viral; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Ganciclovir; Ganciclovir triphosphate; Acyclovir
• Other Study ID Numbers: 20126003312-30; 2012-003312-30 (EudraCT Number)