Evaluation of Acyclovir Infusion on Mortality in Ventilated ICU Patients with Pneumonia and Herpes Simplex Virus Type 1 in Bronchoalveolar Lavage

The primary objective of this study is to evaluate the impact of **acyclovir** therapy on 30-day mortality in patients with lower respiratory tract infection who are on ventilation and have herpes simplex virus type 1 (HSV-1) detected in bronchoalveolar lavage. This is clinically relevant as it aims to determine the potential benefit of antiviral treatment in reducing mortality among critically ill patients with viral co-infection.

Secondary objectives include assessing the following outcomes: - Hospital and intensive care unit length of stay, which provides insight into the healthcare resource utilization and patient recovery trajectory. - HSV-1 eradication, which evaluates the effectiveness of the intervention in eliminating the virus. - Organ dysfunction, which examines the intervention's impact on the overall physiological stability of the patient. - Safety of intervention, which ensures that the treatment does not introduce adverse effects that outweigh its benefits.

The clinical trial involves **patients** in the intensive care unit who are on ventilation and have pneumonia with detection of **herpes simplex virus type 1 (HSV-1)** in bronchoalveolar lavage (BAL). The study population includes both male and female participants aged 18 years and older, who require either invasive or non-invasive respiratory support. Participants must have a PCR HSV-1 detection in BAL with a viral load of at least 10^3 copies/ml and must have pneumonia, which can be community-acquired or healthcare-associated, including ventilator-associated pneumonia. Consent must be provided by the patient or their legal representative. The trial population is considered vulnerable due to their critical health status. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effect of **acyclovir** therapy on the outcome of ventilated patients with lower respiratory tract infection and detection of **herpes simplex virus** type 1 (HSV-1) in bronchoalveolar lavage. This study is a randomized, double-blind, controlled trial with an estimated duration from December 1, 2023, to December 31, 2026. The primary objective is to assess the impact of the intervention on 30-day mortality, with secondary endpoints including ventilation-free days, vasopressor-free days, and various health and quality of life metrics up to 180 days.

Participants will be screened based on inclusion criteria such as being 18 years or older, requiring respiratory support, and having a confirmed PCR detection of HSV-1 in bronchoalveolar lavage. The study will involve multiple visits, starting with an inclusion visit to confirm eligibility and obtain consent. Follow-up visits will occur throughout the treatment period, with assessments at baseline, day 10, and the end of therapy (EOT). The end-of-study visit will evaluate the primary and secondary endpoints, including survival time and quality of life measures.

The expected length of participant involvement is up to 30 days, with the possibility of extending follow-up for certain endpoints up to 180 days. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any situation where continued participation is deemed unsafe by the investigator. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of **aciclovir**, a chemical compound, as the experimental medication. **Aciclovir** is provided in the form of an infusion and is administered intravenously. The maximum daily dose of **aciclovir** is 6000 mg, with a total maximum dose of 60 g over the course of the treatment. The treatment period is limited to a maximum of 10 days. The primary objective of the trial is to assess the impact of **aciclovir** therapy on the 30-day mortality of ventilated patients with lower respiratory tract infections, specifically focusing on the detection of herpes simplex virus in bronchoalveolar lavage.

In addition to the experimental treatment, the study may include the use of standard-of-care therapies as deemed necessary by the clinical investigators. These therapies are not specified in the trial data but are typically administered in accordance with established medical guidelines for the management of lower respiratory tract infections. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed primarily through the evaluation of **30-day mortality** as the primary endpoint. This will involve measuring the survival time of participants from the start of the intervention to 30 days post-treatment. Secondary endpoints will include several parameters to provide a comprehensive assessment of the intervention's impact. These parameters are: ventilation-free days up to day 30, vasopressor-free days until day 30, changes in the Sequential Organ Failure Assessment (SOFA) score and its sub-score for kidney function from baseline to day 10 or end of treatment (EOT), changes in glomerular filtration rate (GFR) from baseline to day 10 or EOT, length of stay in the intensive care unit (ICU) and hospital until day 30, cost of intervention including ICU and hospitalization days plus acyclovir, days without delirium or coma based on the Confusion Assessment Method for the ICU (CAM-ICU) and Richmond Agitation-Sedation Scale (RASS) until day 10 or EOT, microbiological cure defined as the eradication of herpes simplex virus (HSV) in blood and respiratory tract at EOT, and mortality rates at 90 and 180 days. Additionally, quality of life will be assessed using the EQ5D-5L scale at day 10 or EOT, day 30, day 90, and day 180. The incidence of serious adverse events (SAEs) will also be monitored. These efficacy parameters will be collected and analyzed at specified timepoints to determine the impact of acyclovir therapy on patients with lower respiratory tract infections requiring ventilation and HSV detection in bronchoalveolar lavage.