Sildenafil for Hypoxic-ischemic encephalopathy (neonatal)

Inclusion criteria

• {"criterion_text":"- Neonates born at or after 36 weeks’ gestation, treated by therapeutic servo-controlled hypothermia (33.5 +/- 0.5 °C) for neonatal HIE,\n- Experimental treatment will be started > 1h of active hypothermia and <12h of life\n- Social security coverage\n- Informed written consent of one of the two holders of parental authority"}

Exclusion criteria

• {"criterion_text":"- Chromosomal aberrations and major malformations evidenced after birth\n- Decision for “comfort care only” before study drug administration\n- Severe clinical conditions including uncontrolled hemorrhagic syndrome, severe hemodynamic failure at initiation\n- Known hypersensitivity to the active substance or to any of the excipients\n- Concomitant administration of nitrates or nitric oxide donors, Inhaled Nitric Oxide (NO), other PDE5 inhibitors, inhibitors of CYP3A4 (eg, ketoconazole, itraconazole, ritonavir)\n- Participation in another interventional study"}

Primary endpoints

• {"endpoint_text":"- Primary endpoint of step 1 will be the measured plasma concentrations of Sildenafil.","definition_or_measurement_approach":"Measured plasma concentrations of sildenafil (PK plasma concentration measurements)."}
• {"endpoint_text":"- Primary endpoint of step 2 will be survival without brain lesions at hospital discharge on brain MRI. The MRI will be performed between the end of rewarming (day 3.5) and day 5","definition_or_measurement_approach":"Survival without brain lesions assessed by brain MRI performed between end of rewarming (day 3.5) and day 5; assessed at hospital discharge."}

Secondary endpoints

• {"endpoint_text":"- Step 1: estimated clearance parameters and volumes of distribution for IV sildenafil","definition_or_measurement_approach":"PK analysis to estimate clearance parameters and volumes of distribution for IV sildenafil."}
• {"endpoint_text":"- Step 1: area under the plasma sildenafil concentration-time curve and the maximum plasma sildenafil concentration achieved (individual exposure)","definition_or_measurement_approach":"Calculation of AUC and Cmax from plasma concentration-time data (individual exposure)."}
• {"endpoint_text":"- Step 1: brain damage-free survival at hospital discharge on MRIs performed between 3.5 to 5 days and/or 10-30 days” (treatment efficacy)","definition_or_measurement_approach":"Brain damage-free survival assessed on MRIs performed between 3.5–5 days and/or 10–30 days."}
• {"endpoint_text":"- Step 2: Secondary end-points, related to potential benefits, will be based on changes in EEG patterns, detailed analysis of MRIs and spectroscopy, and 2-year assessment (neurodevelopmental impairment, autism spectrum disorders assessed using M-CHAT (Modified Checklist for Autism in Toddlers), PARCA-R and Parenting Stress Index-Short Form (PSI-SF).","definition_or_measurement_approach":"Assessment of EEG changes, detailed MRI and spectroscopy analyses; neurodevelopmental outcomes at 2 years using M-CHAT, PARCA-R and PSI-SF."}
• {"endpoint_text":"- Step 2: Secondary end-points, related to safety, will include incidence of low systemic pressure requiring hemodynamic support, and cardiac function assessment.","definition_or_measurement_approach":"Safety endpoints include incidence of hypotension requiring hemodynamic support and assessments of cardiac function."}

France

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

24-01-2025

Processing Time Days

231

Number Of Sites

6

Number Of Participants

556

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France