A new clinical trial conducted at the Montreal Children’s Hospital (MCH) has found that Viagra, also known as sildenafil, may have the potential to treat newborns who experience oxygen deprivation during pregnancy or at birth. Currently, therapeutic hypothermia is the only treatment option available to prevent brain damage in these cases. However, nearly 29% of babies who undergo this treatment still develop significant neurological problems.
The study, published in The Journal of Pediatrics, is the first of its kind to explore the use of sildenafil in repairing brain damage caused by neonatal encephalopathy. Typically, research focuses on preventive measures rather than treatment. The initial findings suggest that administering sildenafil to babies who experience neurological sequelae despite therapeutic hypothermia is both safe and feasible. Moreover, the study has shown promising signs of efficacy, prompting further research in this area.
Dr. Pia Wintermark, a neonatologist at the MCH and the senior author of the study, believes that having a drug capable of repairing brain damage would be a game-changer for affected babies and their families. Current treatments primarily involve supportive care, such as physiotherapy and specialized care, but a drug that can repair the brain could significantly improve the outlook for these infants.
The idea of using sildenafil in this context emerged while Dr. Wintermark was completing her residency in Switzerland and conducting laboratory experiments in 2010 upon her arrival in Montreal. Subsequently, between 2016 and 2019, Dr. Wintermark and her team were able to proceed with the first phase of the clinical study. This phase involved 24 babies born at 36 weeks of gestation or more, who exhibited moderate to severe neonatal encephalopathy and had already undergone therapeutic hypothermia but still had brain damage.
Of the 24 participants, eight received sildenafil twice a day for seven days, starting on the second or third day of life, while another three received a placebo. The researchers closely monitored the safety of the treatment over the first 10 days of the infants’ lives, recording any adverse events such as hypotension, worsening liver function, and persistent pulmonary hypertension. Although two of the babies experienced a slight decrease in blood pressure after the initial sildenafil dose, this did not recur. One baby who received the drug ultimately died after the family decided to transition to palliative care, but this event was not attributed to the administration of sildenafil. No deaths occurred in the placebo group, confirming the safety of sildenafil for infants with brain damage due to neonatal encephalopathy and who were unresponsive to therapeutic hypothermia.
An exploratory analysis was conducted to assess the efficacy of sildenafil. At 30 days of age, five of the newborns treated with sildenafil showed partial healing of injury, fewer signs of brain volume loss, and an increase in deep gray matter. These positive effects were not observed in the placebo group.
Furthermore, nine out of ten patients from the study underwent neurodevelopmental evaluations at 18 months. Within the sildenafil group, one out of six babies developed cerebral palsy, compared to three out of three babies in the placebo group. Additionally, two out of six children given sildenafil exhibited global developmental and fine motor delays, while all children in the placebo group (three out of three) experienced these delays.
Although the study’s first phase did not aim to establish the efficacy of sildenafil in treating neonatal encephalopathy, the results at 30 days and 18 months have ruled out any long-term adverse events and indicate promising outcomes for future research. Subsequent studies will be conducted with larger cohorts of neonates to validate the phase I findings, determine the optimal dosage of sildenafil, and establish its neuroprotective and neurorestorative potential.
Sildenafil is a cost-effective and easy-to-administer drug. If the drug proves to be effective in the upcoming phases of the study, it has the potential to significantly improve the lives of newborns suffering from neonatal encephalopathy worldwide.