PTH - Preemptive Treatment for Herpesviridae

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Viral Pneumonia

Intervention / Treatment
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* Drug: Aciclovir
* Drug: Ganciclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytomegalovirus, Herpes simplex virus, ICU, mechanical ventilation, mortality, ventilator-free days, PCR