ACICLOVIR for Herpes simplex virus oropharyngeal reactivation

Inclusion criteria

• {"criterion_text":"- aged ≥ 18 year-old\n- Invasive MV for 96 hours and planned to last for at least 48 hours longer\n- HSV reactivation in the throat (qualitative PCR positive for HSV on a throat swab)\n- 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)\n- Written consent from the patient, from a close relative or from the person of trust previously appointed (or inclusion procedure in emergency situations)\n- Under social security cover"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Primary endpoint will be the mortality at day 60 post randomization","definition_or_measurement_approach":"Mortality measured at day 60 post-randomization (all-cause mortality at day 60 after randomization)."}

Secondary endpoints

• {"endpoint_text":"- Day-90 mortality.","definition_or_measurement_approach":"Mortality measured at day 90 post-randomization."}
• {"endpoint_text":"- Duration of mechanical ventilation and ventilator-free days at day 60.","definition_or_measurement_approach":"Duration of mechanical ventilation; ventilator-free days assessed up to day 60 post-randomization."}
• {"endpoint_text":"- ICU length of stay and ICU-free days at day 60.","definition_or_measurement_approach":"ICU length of stay and number of ICU-free days assessed up to day 60 post-randomization."}
• {"endpoint_text":"- Hospital length of stay and hospital-free days at day 60.","definition_or_measurement_approach":"Hospital length of stay and number of hospital-free days assessed up to day 60 post-randomization."}
• {"endpoint_text":"- SOFA score at days 1, 3, 5, 7, 10, 14, 21 and 28 post randomization.","definition_or_measurement_approach":"SOFA score measured at days 1, 3, 5, 7, 10, 14, 21 and 28 after randomization."}
• {"endpoint_text":"- Incidence of HSV oral-labial lesions from randomization to day 28.","definition_or_measurement_approach":"Incidence of herpetic oral-labial lesions from randomization through day 28."}
• {"endpoint_text":"- Rate of patients with HSV positive in the throat at days 3, 7, 10, 14, 17, 21 and 28 post randomization.","definition_or_measurement_approach":"Proportion of patients with HSV positive throat swab (qualitative PCR) assessed at days 3,7,10,14,17,21 and 28 post-randomization."}
• {"endpoint_text":"- Rate of patients with HSV positive in tracheal aspirate at days 1, 7, 14, 21 and 28 post randomization.","definition_or_measurement_approach":"Proportion of patients with HSV positive tracheal aspirate at days 1,7,14,21 and 28 post-randomization."}
• {"endpoint_text":"- Rate of HSV bronchopneumonitis from randomization to day 60 post-randomization","definition_or_measurement_approach":"Incidence of HSV bronchopneumonitis from randomization through day 60."}
• {"endpoint_text":"- Rate of acute respiratory distress syndrome (according to Berlin criteria) from randomization to day 60.","definition_or_measurement_approach":"Incidence of ARDS (Berlin criteria) from randomization through day 60."}
• {"endpoint_text":"- Rate of bacterial ventilator-associated pneumonia from randomization to day 60.","definition_or_measurement_approach":"Incidence of bacterial ventilator-associated pneumonia from randomization through day 60."}
• {"endpoint_text":"- Rate of bacteremia from randomization to day 60.","definition_or_measurement_approach":"Incidence of bacteremia from randomization through day 60."}
• {"endpoint_text":"- Glasgow coma score at days 1, 3, 5, 7, 10, and 14 post-randomization.","definition_or_measurement_approach":"Glasgow Coma Scale measured at days 1,3,5,7,10 and 14 post-randomization."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Creatinine clearance measured at days 1,3,5,7,10,14,21,28; need for renal replacement therapy and RRT-free days assessed from randomization to day 14 (safety for acyclovir)."}
• {"endpoint_text":"- Incidence of adverse event, severe adverse event at days 1, 3, 5, 7, 10, 14, 21 and 28 post randomization.","definition_or_measurement_approach":"Incidence and severity of adverse events and serious adverse events assessed at days 1,3,5,7,10,14,21 and 28 post-randomization."}

France

Earliest CTIS Part Ii Submission Date

13-12-2023

Latest Decision Or Authorization Date

19-04-2024

Processing Time Days

128

Number Of Sites

6

Number Of Participants

246

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France