Oral Sildenafil Citrate to Improve Maternal and Neonatal Outcomes in Low-resource Settings

Overview

The goal of this feasibility pilot clinical trial is to determine if sildenafil citrate 50mg orally, up to three times during labor, can: 1) reduce perinatal mortality and/or bag and mask ventilation at birth in planned vaginal delivery and 2) reduce the incidence of operative delivery (instrumental vaginal birth or emergency cesarean section) for presumed or suspected fetal distress in up to four facilities of different levels of care in low-resource countries. The main questions it aims to answer are: Does sildenafil citrate decrease: 1. the incidence of operative delivery (instrumental vaginal birth or emergency cesarean section) for presumed or suspected fetal distress? 2. the incidence of bag and mask ventilation? 3. the incidence of perinatal mortality? Researchers will compare sildenafil citrate to a placebo (a look-alike substance that contains no drug) to see if sildenafil works to prevent fetal distress necessitating operative delivery, bag and mask resuscitation at birth, and ultimately, perinatal mortality. Participants will: 1. Take Sildenafil 50 mg or placebo orally every eight hours during labor (up to 3 doses) 2. Have the (mothers and babies) medical charts reviewed for outcomes, including fetal distress, operative delivery, maternal side effects, neonatal bag \& mask ventilation, Apgar Scores, and seizures. 3. Have a neonatal neurological assessment prior to discharge 4. Receive telephone call assessments for re-hospitalization or mortality 7 days post delivery The results of this feasibility pilot trial will be used to inform the design and conduct of a large pragmatic randomized controlled trial to determine if sildenafil citrate, compared to placebo, will decrease fetal distress and perinatal asphyxia.

Pregnant women with planned vaginal deliveries will be screened for eligibility. After informed consent obtained, subjects will be randomly assigned (using computer generated, stratified randomization codes by the pharmacy) to either the treatment arm (Sildenafil citrate) or the placebo concurrent control. Clinicians, researchers, and primary caregivers will be masked. Eligible women will be randomized to receive sildenafil 50 mg orally every 8 hours up to a total of 3 doses or to receive the placebo every 8 hours up to a total of 3 does during the course of labor. Neither medication no placebo will be given following completion of labor. All additional care of the mother and infant will be provided according to the local standard of care. A neurological examination (Sarnat and Thompson) will be completed on the infant within 24 hours after birth. Neonatal oxygen saturation will be measured by pulse oximetry at 48 hours or discharge, whichever comes first. Outcomes will be collected following delivery, discharge, and 7-days post-partum. 7-day follow-up for outcomes will be obtained via a telephone call.