Effect of acyclovir therapy on the outcome of ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Friedrich Schiller Universitaet Jena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Virus Diseases [C02]

Trial duration

10 Jan 2024 → ongoing

Decision date (initial)

2023-09-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bundesministerium für Bildung und Forschung (BMBF)

External identifiers

EU CT number

2023-504322-19-00

ClinicalTrials.gov

NCT06134492

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Testing the impact of the intervention on mortality (30-day mortality).

Secondary objectives 4

1. Hospital and intensive care unit length of stay
2. HSV-1 eradication
3. Organ dysfunction
4. Safety of intervention

Conditions and MedDRA coding

Patients in the intensive care unit on ventilation with pneumonia and detection of herpes simplex virus type 1 (HSV-1) in bronchoalveolar lavage (BAL).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 8

1. History of hypersensitivity to acyclovir or valacyclovir or other components of the investigational product
2. Pregnancy/Lactation
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 30-day mortality (Survival time)

Secondary endpoints 14

1. Ventilation-free days up to day 30 (days without invasive ventilation via endotracheal tube, incl. tracheostoma as well as without non-invasive ventilation)
2. Vasopressor-free days until day 30 (days without continuous vasopressor administration > 1h/day)
3. Delta SOFA (Baseline - Day 10 or EOT)
4. Delta SOFA sub-score kidney (baseline - day 10 or EOT)
5. Delta GFR value (baseline - day 10 or EOT)
6. Length of stay in ICU until day 30
7. Length of stay in Hospital until day 30
8. Cost of intervention (ICU and hospitalization days + acyclovir)
9. Days without delirium/coma (based on CAM-ICU / RASS) until day 10/end of therapy
10. Microbiological cure (EOT) - HSV eradication for blood and respiratory tract respectively (no HSV detectable in PCR test at end of therapy)
11. 90 days mortality
12. 180 days mortality
13. Quality of life (EQ5D-5L) day 10 or EOT, day 30, day 90, and day 180.
14. Incidence SAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Friedrich Schiller Universitaet Jena

Sponsor organisation

Friedrich Schiller Universitaet Jena

Address

Am Klinikum 1, Lobeda Lobeda

City

Jena

Postcode

07747

Country

Germany

Scientific contact point

Organisation

Friedrich Schiller Universitaet Jena

Contact name

Stefan Hagel

Public contact point

Organisation

Friedrich Schiller Universitaet Jena

Contact name

Stefan Hagel

Third parties 1

Locations

1 EU/EEA country · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications