Acyclovir in Ventilated Patients With Pneumonia and HSV-1 in BAL (HerpMV)

July 22, 2026 updated by: Stefan Hagel, Jena University Hospital

Effect of Acyclovir Therapy on the Outcome of Ventilated Patients With Lower Respiratory Tract Infection and Detection of Herpes Simplex Virus in Bronchoalveolar Lavage

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

616

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bielefeld, Germany, 33611
        • Recruiting
        • Evangelisches Klinikum Bethel
        • Principal Investigator:
          • Friedhelm Bach, Dr.
        • Contact:
    • Baden-Wurttemberg
      • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
        • Recruiting
        • Universitätsklinikum Freiburg
        • Contact:
        • Principal Investigator:
          • Paul Biever, Dr.
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
        • Recruiting
        • Universitatsklinikum Heidelberg
        • Contact:
        • Principal Investigator:
          • Tobias Gutting, Dr.
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Recruiting
        • Universitätsklinikum Tübingen
        • Contact:
        • Principal Investigator:
          • Peter Rosenberger, Prof. Dr.
    • Bavaria
      • Augsburg, Bavaria, Germany, 86156
        • Recruiting
        • Universitätsklinikum Augsburg
        • Contact:
        • Principal Investigator:
          • Phillip Simon, Prof. Dr.
      • München, Bavaria, Germany, 81675
        • Recruiting
        • Klinikum rechts der Isar
        • Contact:
        • Principal Investigator:
          • Tobias Lahmer, Dr.
      • München, Bavaria, Germany, 81377
        • Recruiting
        • Klinikum der Ludwig-Maximilian-Universität München
        • Contact:
        • Principal Investigator:
          • Michael Zoller, Dr.
      • Nuremberg, Bavaria, Germany, 90419
        • Recruiting
        • Klinikum Nürnberg, Campus Nord
        • Contact:
        • Principal Investigator:
          • Arnim Geise, Dr.
      • Nuremberg, Bavaria, Germany, 90471
        • Recruiting
        • Klinikum Nürnberg, Campus Süd
        • Contact:
        • Principal Investigator:
          • Silke Fortenbacher, Dr.
      • Regensburg, Bavaria, Germany, 93053
      • Rosenheim, Bavaria, Germany, 83022
        • Recruiting
        • RoMed Klinikum Rosenheim
        • Contact:
        • Principal Investigator:
          • Balázs Poros, Dr.
    • Free and Hanseatic City of Hamburg
      • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg Eppendorf
        • Contact:
          • Stefan Kluge, Prof. Dr.
          • Phone Number: 040741057010
          • Email: s.kluge@uke.de
        • Principal Investigator:
          • Stefan Kluge, Prof. Dr.
    • Nordreihn-Westfalen
      • Herne, Nordreihn-Westfalen, Germany, 44625
        • Recruiting
        • Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum
        • Principal Investigator:
          • Ulrich Frey, Prof. Dr. med.
        • Contact:
    • North Rhine-Westphalia
      • Bielefeld, North Rhine-Westphalia, Germany, 33617
        • Recruiting
        • Evangelisches Klinikum Bethel
        • Contact:
        • Principal Investigator:
          • Friedhelm Bach, Dr.
      • Bonn, North Rhine-Westphalia, Germany, 53127
        • Recruiting
        • Universitätsklinikum Bonn
        • Principal Investigator:
          • Christian Putensen, Prof. Dr.
        • Contact:
      • Cologne, North Rhine-Westphalia, Germany, 50937
        • Recruiting
        • Universitätsklinikum Köln AöR
        • Contact:
        • Principal Investigator:
          • Fabian Dusse, Dr.
      • Düsseldorf, North Rhine-Westphalia, Germany, 40225
        • Recruiting
        • Universitätsklinikum Düsseldorf
        • Contact:
        • Principal Investigator:
          • Christian Jung, Prof. Dr.
      • Essen, North Rhine-Westphalia, Germany, 45147
        • Recruiting
        • Universitatsklinikum Essen
        • Principal Investigator:
          • Thorsten Brenner, Prof. Dr. med.
        • Contact:
      • Münster, North Rhine-Westphalia, Germany, 48149
        • Recruiting
        • Universitatsklinikum Munster
        • Principal Investigator:
          • Christian Ertmer, Prof. Dr.
        • Contact:
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Recruiting
        • Universitätsklinikum Dresden
        • Principal Investigator:
          • Andreas Güldner, Dr. med.
        • Contact:
      • Leipzig, Saxony, Germany, 04103
        • Recruiting
        • Universitätsklinikum Leipzig
        • Contact:
        • Principal Investigator:
          • Gunther Hempel, Dr.
    • Saxony-Anhalt
      • Halle, Saxony-Anhalt, Germany, 06120
        • Recruiting
        • Universitätsklinikum Halle
        • Contact:
        • Principal Investigator:
          • Alexander Vogt, Dr.
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Recruiting
        • Universitätsklinikum Schleswig-Holstein Campus Kiel
        • Contact:
        • Principal Investigator:
          • Matthias Lindner, Dr.
      • Lübeck, Schleswig-Holstein, Germany, 23538
        • Recruiting
        • Universitätsklinikum Schleswig-Holstein Campus Lübeck
        • Contact:
        • Principal Investigator:
          • Maria Deja, Prof. Dr.
    • Thuringia
      • Jena, Thuringia, Germany, 07747

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Criteria:

  1. History of hypersensitivity to acyclovir or valacyclovir or other components of the investigational product.
  2. Pregnancy/Lactation 3.3. Simultaneous participation in another clinical interventional trial under EU Regulation 536/2014, the German Medicines Act (AMG), Medical Devices Regulation (MDR), or Medical Devices Act (MPDG) without prior consultation and approval by the respective sponsors prior to randomization

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment group
Aciclovir therapy
Drug: Acyclovir

Dosage: 10mg/kg (current) body weight every 8 hours, dose adjustment to renal function according to technical information.

Mode of administration: intravenous (i.v.)

Other Names:
  • Aciclovir
No Intervention: Comparison group
No study-specific treatment measures

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mortality (survival status)
Time Frame: day 30
survival status
day 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilation-free days
Time Frame: day 30
days without mechanically ventilation via endotracheal tube, incl. tracheostoma
day 30
Vasopressor-free days
Time Frame: day 30
days without continuous vasopressor administration > 1h/day
day 30
Delta SOFA score (Sepsis-related Organ Failure Assessment Score)
Time Frame: Baseline - Day 10 or EOT if this event occurs earlier
Each of six organ systems receive a score ranging from 0 (normal) to 4 (most abnormal), with a minimum SOFA score of 0 and a maximum SOFA score of 24
Baseline - Day 10 or EOT if this event occurs earlier
Delta SOFA sub-score kidney (Sepsis-related Organ Failure Assessment Score)
Time Frame: Baseline - Day 10 or EOT if this event occurs earlier
Sub-score for kidney function, the score ranges from 0 (normal) to 4 (most abnormal)
Baseline - Day 10 or EOT if this event occurs earlier
Delta GFR value
Time Frame: Baseline - Day 10 or EOT if this event occurs earlier
GFR value
Baseline - Day 10 or EOT if this event occurs earlier
Length of stay in ICU
Time Frame: day 30
days LOS in ICU
day 30
Length of stay in Hospital
Time Frame: day 30
days LOS in hospital
day 30
Cost of intervention
Time Frame: up to day 90
ICU and hospitalization days + acyclovir
up to day 90
Days without delirium/coma
Time Frame: Until day 10 or until EOT if this event occurs earlier
based on CAM-ICU / RASS
Until day 10 or until EOT if this event occurs earlier
Microbiological cure (EOT)
Time Frame: At day 10 or day of EOT if this event occurs earlier
Percent of participants with HSV eradication (PCR testing negative) in blood and respiratory tract
At day 10 or day of EOT if this event occurs earlier
mortality (survival status)
Time Frame: 90 days
survival status
90 days
mortality (survival status)
Time Frame: 180 days
survival status
180 days
Quality of life (EQ-5D-5L)
Time Frame: Measurement at day 10 or EOT if this event occurs earlier, day 30, day 90, and day 180
EuroQuality of Life Five Dimensions (EQ-5D-5L), the descriptive system comprises five dimensions (MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION), with five response levels: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems.
Measurement at day 10 or EOT if this event occurs earlier, day 30, day 90, and day 180
Incidence SAEs
Time Frame: From time of randomization until day 10 or EOT if this event occurs earlier
Incidence of serious adverse events
From time of randomization until day 10 or EOT if this event occurs earlier

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jena University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 1, 2023

First Submitted That Met QC Criteria

November 10, 2023

First Posted (Actual)

November 18, 2023

Study Record Updates

Last Update Posted (Actual)

July 23, 2026

Last Update Submitted That Met QC Criteria

July 22, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZKSJ0153
  • BMBF 01KG2301 (Other Grant/Funding Number: Federal Ministry of Education and Research)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Results will be published in a journal indexed in MEDLINE and CTIS; there are no publication restrictions. After publication, deidentified, individual participant data that underlie this trial, along with a data dictionary describing variables in the dataset, will be made available to researchers whose proposed purpose of use is approved by the Trial Management Team.

IPD Sharing Time Frame

After publication

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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