Sildenafil Plus Hypothermia to Treat Neonatal Encephalopathy

Summary

The main objective of this study is to assess pharmacokinetics features of IV sildenafil in neonates with hypoxic-ischemic encephalopathy and treated by controlled hypothermia. This phase 2 study will prepare a large phase 3 randomized controlled trial to demonstrate the superiority of a combinatory therapy associating IV sildenafil and controlled hypothermia compared to Placebo and controlled hypothermia, on survival without brain lesions on MRI at discharge, in neonates born after 36 weeks of gestation.

Timeline

Start

2026-10

Primary completion

2027-06

Completion

2029-05

Publications

• Results Yazdani A, Howidi B, Shi MZ, Tugarinov N, Khoja Z, Wintermark P. Sildenafil improves hippocampal brain injuries and restores neuronal development after neonatal hypoxia-ischemia in male rat pups. Sci Rep. 2021 Nov 11;11(1):22046. doi: 10.1038/s41598-021-01097-6.
• Results Yazdani A, Khoja Z, Johnstone A, Dale L, Rampakakis E, Wintermark P. Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups. Dev Neurosci. 2016;38(4):251-263. doi: 10.1159/000448327. Epub 2016 Sep 10.
• Results Moretti R, Leger PL, Besson VC, Csaba Z, Pansiot J, Di Criscio L, Gentili A, Titomanlio L, Bonnin P, Baud O, Charriaut-Marlangue C. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain. J Neuroinflammation. 2016 Apr 28;13(1):95. doi: 10.1186/s12974-016-0560-4.
• Results Charriaut-Marlangue C, Nguyen T, Bonnin P, Duy AP, Leger PL, Csaba Z, Pansiot J, Bourgeois T, Renolleau S, Baud O. Sildenafil mediates blood-flow redistribution and neuroprotection after neonatal hypoxia-ischemia. Stroke. 2014 Mar;45(3):850-6. doi: 10.1161/STROKEAHA.113.003606. Epub 2014 Jan 28.

Drugs

Indications