Preemptive Treatment With Acyclovir in Intubated and Mechanically Ventilated Patients With Herpes (PTH2)

NCT06217406 | Not Yet Recruiting

• 2 other identifiers: APHP2208002023-505510-26-00
• Study Type: interventional
• Target: 246
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research aims to assess the interest of preemptive treatment with Acyclovir in mechanically ventilated patients with reactivation of Herpes simplex (HSV) in the throat and failure of one organ or less. HSV reactivation is common in patients hospitalized in an intensive care unit (ICU) on invasive mechanical ventilation. It begins at the oropharyngeal level (incidence up to 20-50%), then progresses downward with contamination of the distal airways (reported incidence of 20-65%). HSV reactivation is associated with high mortality. The investigators aim to disable that, in mechanically ventilated patients with HSV reactivation in the throat and failure of one organ or less, preemptive treatment with Acyclovir may reduce mortality. To answer the question posed in the research, it is planned to include 246 people hospitalized in intensive care on invasive mechanical ventilation, presenting with HSV reactivation of the throat and one organ failure or less.

Conditions

Invasive Mechanical Ventilation; HSV Throat Reactivation

Keywords

ICU; invasive mechanical ventilation; HSV; Acyclovir; Preemptive treatment

Outcome Measures

Primary Outcomes (1)

• Mortality

  Primary endpoint will be the mortality at day 60 post randomization

  day 60

Secondary Outcomes (20)

• Mortality

  Vital status at day 90 will be assessed either by visit if the patient is still in the hospital, or by phone is the patient is discharged from the hospital

• Duration of mechanical ventilation

  from date of randomization until the date of extubation or death, whichever first occurs, up to 60 days

• Ventilator-free days at day 60

  day 60 post-randomization

• ICU length of stay

  from date of randomization until the date of ICU discharge or death, up to 60 days

• ICU-free days

  day 60 post-randomization

Study Arms (2)

ACYCLOVIR

EXPERIMENTAL

Intravenous acyclovir (ACYCLOVIR )

Drug: Intravenous acyclovir (ACYCLOVIR )

PLACEBO

PLACEBO COMPARATOR

saline bags

Drug: Saline bags

Interventions

Intravenous acyclovir (ACYCLOVIR ) DRUG

Patients randomized in the experimental arm will receive intravenous acyclovir at a dosing of 5 mg/kg/8 hours during 14 days (treatment will be stopped at ICU discharge).

ACYCLOVIR

Saline bags DRUG

Patients randomized in the control arm will receive placebo, eg. saline bags (same volume as acyclovir bags) every 8 hours during 14 days (treatment will be stopped in case of ICU discharge).

PLACEBO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged ≥ 18 year-old
• invasive mechanical ventilation(MV) for 96 hours and planned to last for at least 48 hours longer
• HSV reactivation in the throat (qualitative PCR positive for HSV on a throat swab)
• Presence of 1 or less organ failure; organ failure being defined as a corresponding-organ SOFA score of 3 or 4 (for example, renal failure will be defined as a renal SOFA score of 3 or 4)
• Effective contraception for patients of childbearing age, throughout the treatment period
• Under social security cover

You may not qualify if:

• Hypersensitivity to acyclovir and excipient
• Pregnant or breastfeeding (controlled by a blood pregnancy test)
• Patient who received an antiviral drug active against HSV (acyclovir, valacyclovir, gancyclovir, valgancyclovir, foscavir, cidofovir) in the previous 30 days
• Duration of ventilation before randomization \>15 days
• Neutropenia, defined by an absolute neutrophils count \< 1,000/mm3
• Solid organ or bone-marrow transplant
• Immunosuppressive treatment (including steroids at a dose \>0.5 mg/kg/day of prednisone or equivalent for \>1 month)
• HIV infection
• Decision of withholding/withdrawing care

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Interventions

Acyclovir

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Charles-Edouard LUYT, Pr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charles-Edouard LUYT, Pr

CONTACT

(0)142163824; charles-edouard.luyt@aphp.fr

Anne BISSERY

CONTACT

(0)142162432

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 22, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 22, 2024

Record last verified: 2024-01