Preemptive Treament with acyclovir in intubated and mechanically ventilated patients with Herpes simplex virus oropharyngeal reactivation and one or less organ failure (PTH2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

19 Jun 2024 → ongoing

Decision date (initial)

2024-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévention

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

The primary objective is to show that, in mechanically-ventilated patients hospitalized in the ICU with HSV throat reactivation and 1 organ failure or less, a treatment with acyclovir reduces mortality at day 60 as compared to a placebo.

Secondary objectives 12

1. To show the efficacy of a treatment with acyclovir as compared to placebo on duration of mechanical ventilation
2. To show the efficacy of a treatment with acyclovir as compared to placebo on ICU and hospital length of stay.
3. To show the efficacy of a treatment with acyclovir as compared to placebo on kinetics of organs failures from randomization to day 14
4. To show the efficacy of a treatment with acyclovir as compared to placebo on incidence of herpetic oral-labial lesions
5. To show the efficacy of a treatment with acyclovir as compared to placebo on duration of HSV oropharyngeal shedding
6. To show the efficacy of a treatment with acyclovir as compared to placebo on incidence of HSV colonization of lower respiratory tract after randomization
7. To show the efficacy of a treatment with acyclovir as compared to placebo on incidence of HSV bronchopneumonitis
8. To show the efficacy of a treatment with acyclovir as compared to placebo on incidence of acute respiratory distress syndrome.
9. To show the efficacy of a treatment with acyclovir as compared to placebo on incidence of nosocomial infections (pneumonia, blood stream infections).
10. To demonstrate the safety of a treatment with acyclovir as compared to placebo on neurological toxicity
11. To demonstrate the safety of a treatment with acyclovir as compared to placebo on renal toxicity (Creatinine clearance, Need for renal replacement therapy)
12. To demonstrate the safety of a treatment with acyclovir as compared to placebo on frequency and intensity of adverse event and severe adverse event.

Conditions and MedDRA coding

Patients in ICU with invasive mechanical ventilation and HSV throat reactivation with 1 or no organ failures.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. aged ≥ 18 year-old
2. Invasive MV for 96 hours and planned to last for at least 48 hours longer
3. HSV reactivation in the throat (qualitative PCR positive for HSV on a throat swab)
4. Presence of 1 or less organ failure; organ failure being defined as a corresponding-organ SOFA score of 3 or 4 (for example, renal failure will be defined as a renal SOFA score of 3 or 4)
5. Written consent from the patient, from a close relative or from the person of trust previously appointed (or inclusion procedure in emergency situations)
6. Under social security cover

Exclusion criteria 10

1. Hypersensitivity to acyclovir, to valacyclovir or to excipient
2. Pregnant or breastfeeding (controlled by a urinary or blood pregnancy test)
3. Patient who received an antiviral drug active against HSV (acyclovir, valacyclovir, gancyclovir, valgancyclovir, foscarvir, cidofovir) in the previous 30 days
4. Duration of ventilation before randomization >15 days
5. Neutropenia, defined by an absolute neutrophils count < 1,000/mm3
6. Solid organ or bone-marrow transplant
7. Immunosuppressive treatment (including steroids at a dose >0.5 mg/kg/day of prednisone or equivalent for >1 month)
8. HIV infection
9. Moribund, defined by a SAPS II score at inclusion >75 points
10. Decision of withholding/withdrawing care

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint will be the mortality at day 60 post randomization

Secondary endpoints 15

1. Day-90 mortality.
2. Duration of mechanical ventilation and ventilator-free days at day 60.
3. ICU length of stay and ICU-free days at day 60.
4. Hospital length of stay and hospital-free days at day 60.
5. SOFA score at days 1, 3, 5, 7, 10, 14, 21 and 28 post randomization.
6. Incidence of HSV oral-labial lesions from randomization to day 28.
7. Rate of patients with HSV positive in the throat at days 3, 7, 10, 14, 17, 21 and 28 post randomization.
8. Rate of patients with HSV positive in tracheal aspirate at days 1, 7, 14, 21 and 28 post randomization.
9. Rate of HSV bronchopneumonitis from randomization to day 60 post-randomization
10. Rate of acute respiratory distress syndrome (according to Berlin criteria) from randomization to day 60.
11. Rate of bacterial ventilator-associated pneumonia from randomization to day 60.
12. Rate of bacteremia from randomization to day 60.
13. Glasgow coma score at days 1, 3, 5, 7, 10, and 14 post-randomization.
14. Creatinine clearance at days 1, 3, 5, 7, 10, 14, 21 and 28 post randomization and need for renal replacement therapy and RRT free days from randomization to day 14 (acyclovir toxicity)
15. Incidence of adverse event, severe adverse event at days 1, 3, 5, 7, 10, 14, 21 and 28 post randomization.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 6 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 4 files

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

Application history

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