Acyclovir in Ventilated Patients With Pneumonia and HSV-1 in BAL

Last updated: April 4, 2025
Sponsor: Jena University Hospital
Overall Status: Active - Recruiting

Phase

3

Condition

Respiratory Syncytial Virus (Rsv) Infection

Pneumonia (Pediatric)

Pneumonia

Treatment

Acyclovir

Clinical Study ID

NCT06134492
ZKSJ0153
BMBF 01KG2301
  • Ages > 18
  • All Genders

Study Summary

Almost 90 out of 100 people carry herpes simplex viruses (HSV). Once a person has been infected with the herpes viruses, he or she can't get rid of them for the rest of her/his life. For the most part, the viruses are in a dormant state. Only when the immune system is weakened, for example in the case of a serious illness or stress, are the viruses reactivated. They then mainly cause cold sores, which are harmless for healthy people and usually heal without therapy. However, especially in people with a weakened immune system, HSV can also cause serious infections, such as meningitis. In almost every second mechanically ventilated patient in intensive care who has pneumonia, HSV can be detected in the respiratory tract. This is caused by reactivation of the viruses as a result of the severe underlying disease and stress during intensive care therapy. Whether treatment of the herpes viruses (e.g. with acyclovir) is necessary in this situation and helps the patients to cure has not been clarified, especially as acyclovir can also cause side effects such as a deterioration in kidney function. Currently, the physicians decide to treat the herpes viruses in about half of the patients. Several studies have shown that patients for whom the physician decided to treat the viruses survived more often. However, all of these studies looked at the course of the disease only retrospectively and thus are subject to many biases (including physician selection of who receives treatment, missing data). A definitive conclusion as to whether herpesvirus therapy can be recommended cannot be drawn without doubt from these studies. Therefore, the investigators would like to investigate in a randomized controlled trial, i.e. patients are randomly assigned to the experimental (therapy of herpesviruses) or control group (no therapy of herpesviruses), the effect of therapy with acyclovir on survival in ventilated intensive care patients with lower respiratory tract infection (pneumonia) in whom a large amount of HSV was found in the respiratory tract. The goal of the study is to provide clarity on whether therapy will help patients recover.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. ≥ 18 years

  2. need for invasive or non-invasive respiratory support

  3. PCR HSV-1 detection in BAL (≥ 10^3 copies/ml)

  4. Pneumonia (community or healthcare acquired, incl. ventilator-associated pneumonia)

  5. declaration of consent by the patient or legal representative

Exclusion

Exclusion Criteria:

  1. History of hypersensitivity to acyclovir or valacyclovir or other components of theinvestigational product.

  2. Pregnancy/Lactation

  3. Simultaneous participation in another interventional clinical trial

  4. Decision to withhold life-sustaining therapies

  5. Use of a virostatic agent (i.v. or p. os) with activity against herpes simplex (acyclovir, valacyclovir, famciclovir/penciclovir, brivudine, cidofovir, foscarnet)for therapeutic or prophylactic reasons at the time of randomization.

  6. Solid organ transplantation, stem cell transplantation

  7. Neutropenia (absolute neutrophil count <1500/μl (<1.5 × 109 /l)

  8. Previous study participation in HerpMV

Study Design

Total Participants: 616
Treatment Group(s): 1
Primary Treatment: Acyclovir
Phase: 3
Study Start date:
February 20, 2024
Estimated Completion Date:
December 31, 2026

Study Description

Herpes-simplex virus (HSV) can be detected in the bronchoalveolar lavage (BAL) in up to 60% of mechanically ventilated (MV) ICU patients with a lower respiratory tract infection (LRTI), depending on the study population and the severity of disease. However, it remains unclear whether the detection represents a harmless viral shedding as a consequence of reactivation, reflecting the severity of the underlying disease and immunoparalysis, or a true clinical infection requiring antiviral therapy. To date, only retrospective studies have investigated the benefit of an antiviral therapy in HSV-positive ICU patients on mechanical ventilation (MV) with LRTI. In a retrospective study and additional meta-analysis on this topic a antiviral treatment was associated with an improved patient outcome, i.e.; lower all-cause hospital mortality (RR 0.74, 95% CI 0.64-0.85) and lower 30-day all-cause mortality (RR 0.75, 95% CI 0.59-0.94; 3 studies). Aim of this study is to determine prospectively in a multicenter, randomized controlled trial whether acyclovir therapy improves outcome in ventilated ICU patients with a LRTI and HSV detection in BAL. Overall, 616 ICU patients with MV and LRTI and HSV1-PCR-detection in BAL (>= 10E3 copies/ml) will be either randomized to receive acyclovir (10mg/kg body weight tid) for 10 days (or discharge from ICU if this is earlier) or no antiviral therapy (control group). Primary efficacy endpoint will be overall survival within 30 days comparing the acyclovir therapy and the control group. Secondary endpoints include ventilation-free days up to day 30, vasopressor-free days until day 30 and safety.

Connect with a study center

  • Universitätsklinikum Freiburg

    Freiburg, Baden-Württemberg 79106
    Germany

    Active - Recruiting

  • Universitätsklinikum Heidelberg

    Heidelberg, Baden-Württemberg 69120
    Germany

    Active - Recruiting

  • Universitätsklinikum Tübingen

    Tübingen, Baden-Württemberg 72076
    Germany

    Active - Recruiting

  • Universitätsklinikum Augsburg

    Augsburg, Bayern 86156
    Germany

    Active - Recruiting

  • Klinikum der Ludwig-Maximilian-Universität München

    München, Bayern 81377
    Germany

    Active - Recruiting

  • Klinikum rechts der Isar

    München, Bayern 81675
    Germany

    Active - Recruiting

  • Klinikum Nürnberg, Campus Nord

    Nürnberg, Bayern 90419
    Germany

    Active - Recruiting

  • Klinikum Nürnberg, Campus Süd

    Nürnberg, Bayern 90471
    Germany

    Active - Recruiting

  • Universitätsklinikum Regensburg

    Regensburg, Bayern 93053
    Germany

    Active - Recruiting

  • RoMed Klinikum Rosenheim

    Rosenheim, Bayern 83022
    Germany

    Active - Recruiting

  • Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum

    Herne, Nordreihn-Westfalen 44625
    Germany

    Active - Recruiting

  • Evangelisches Klinikum Bethel

    Bielefeld, Nordrhein-Westfalen 33617
    Germany

    Active - Recruiting

  • Universitätsklinikum Bonn

    Bonn, Nordrhein-Westfalen 53127
    Germany

    Active - Recruiting

  • Universitätsklinikum Düsseldorf

    Düsseldorf, Nordrhein-Westfalen 40225
    Germany

    Active - Recruiting

  • Universitätsklinikum Essen

    Essen, Nordrhein-Westfalen 45147
    Germany

    Active - Recruiting

  • Universitätsklinikum Köln AöR

    Köln, Nordrhein-Westfalen 50937
    Germany

    Active - Recruiting

  • Universitätsklinikum Münster

    Münster, Nordrhein-Westfalen 48149
    Germany

    Active - Recruiting

  • Universitätsklinikum Dresden

    Dresden, Sachsen 01307
    Germany

    Active - Recruiting

  • Universitätsklinikum Leipzig

    Leipzig, Sachsen 04103
    Germany

    Active - Recruiting

  • Universitätsklinikum Halle

    Halle, Sachsen-Anhalt 06120
    Germany

    Active - Recruiting

  • Universitätsklinikum Schleswig-Holstein Campus Kiel

    Kiel, Schleswig-Holstein 24105
    Germany

    Active - Recruiting

  • Universitätsklinikum Schleswig-Holstein Campus Lübeck

    Lübeck, Schleswig-Holstein 23538
    Germany

    Active - Recruiting

  • SRH Wald Klinikum Gera

    Gera, Thüringen 07548
    Germany

    Site Not Available

  • Universitätsklinikum Jena

    Jena, Thüringen 07747
    Germany

    Active - Recruiting

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246
    Germany

    Active - Recruiting

  • Westfälische Wilhelms-Universität

    Münster, 48149
    Germany

    Active - Recruiting

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