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

ZKSJ0153

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 mechanically 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.

2024-02-20

2026-07-01

2026-12-01

Recruiting

Early phase I

710

Inclusion Criteria: 1. ≥ 18 years 2. Invasive ventilation expected for ≥ 48 hours from time of randomization 3. PCR HSV-1 detection in BAL (\>=10E5 copies/ml). 4. Pneumonia (community or healthcare acquired, incl. ventilator-associated pneumonia) 5. Written 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. 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 (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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 710, 'type': 'ESTIMATED'}}

2024-04-29