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

Oral Sildenafil Citrate to Improve Maternal and Neonatal Outcomes in Low-resource Settings: A Randomized Pilot Feasibility Trial

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.

Study Overview

• Status: Withdrawn
• Conditions: Neonatal Asphyxia; Intrapartum Fetal Distress; Intrapartum Asphyxia; Instrumental Delivery; Affecting Fetus
• Intervention / Treatment: Drug: Sildenafil 50 mg Oral Tablet; Drug: Placebo Oral Tablet

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Nigeria
  • Lagos
    • Lagos, Lagos, Nigeria, 101001
      • Lagos Island Maternity Hospital
    • Lagos, Lagos, Nigeria, 102215
      • University Teaching Hospital, University of Lagos
    • Surulere, Lagos, Nigeria, 101241
      • Mother and Child Hospital
  • Oyo State
    • Ogbomoso, Oyo State, Nigeria, 210271
      • Ladoke Akintola University of Technology Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pregnant women presenting in early labor with a term pregnancy (≥ 37 weeks to 41wks 6days gestation )

   • Early labor will be defined as cervical dilation less than 7cm
   • Gestational age will be calculated from the most reliable variable using the following hierarchy of reliability: 2) gestational dating ultrasound completed at any time during the pregnancy (with preference to the earliest exam); 2) date of last menstrual period if menses are regular.
2. Planned vaginal delivery and admission to health facility with clear plan for spontaneous or induced vaginal delivery
3. Maternal age ≥ 18yrs

Exclusion Criteria:

1. Unknown gestational age
2. Non-cephalic fetal presentation
3. Plan for cesarean delivery prior to enrollment
4. Previous uterine scar (cesarean section and/or myomectomy)
5. Advanced stage of labor (7 cm or greater cervical dilation per local standards) and pushing, or too distressed to understand, confirm, or give informed consent regardless of cervical dilation
6. Not capable of giving consent due to other health problems, such as obstetric emergencies (i.e. antepartum hemorrhage) or mental disorder
7. Maternal contraindication to sildenafil therapy, such as hypersensitivity to nitrates or nitrites
8. Recognized major structural fetal anomaly
9. Previous randomization in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Sildenafil 50mg; Sildenafil citrate 50mg given orally every eight hours up to 3 doses while mother is in labor	Drug: Sildenafil 50 mg Oral Tablet; Sildenafil 50 mg given orally every eight hours up to three times while mother is in labor; Other Names: Revatio
Placebo Comparator: Placebo; Identical-appearing treatment that does not contain the test drug given orally every eight hours up to 3 doses while mother is in labor	Drug: Placebo Oral Tablet; Placebo tablet given orally every eight hours up to three times while mother is in labor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of perinatal mortality	Documentation of stillbirth or neonatal death	96 hours after enrollment
Percentage of operative delivery	Documentation of type of delivery	96 hours after enrollment
Indication for operative delivery	Documentation of type of delivery	96 hours after enrollment
Percentage of use of bag and mask in neonates after delivery	Documentation of the use of bag and mask ventilation as resuscitation after delivery	20 minutes after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of mothers who received fetal heart rate monitoring	Documentation of rate of heart rate monitoring	96 hours after enrollment
Indication for fetal heart rate monitoring	Documentation of the indication for use of fetal heart rate monitoring	96 hours after enrollment
Apgar Score	Documentation of Apgar score at 1 minute and 5 minutes (Value 0-10, with 10 meaning better outcome)	1 minute and 5 minutes after birth
Percentage of neonates with hypoxemia	Documentation of saturations < 95% measured by noninvasive pre/post pulse oximetry	48 hours after birth or at discharge, if early discharge
Percentage of infants with neonatal hypoxic-ischemic encephalopathy	Documentation of neonatal encephalopathy	96 hours after enrollment
Percentage of neonatal ICU admissions	Documentation of admission to the Neonatal Intensive Care Unit or comparable level of care	96 hours after enrollment
Percentage of maternal rehospitalization	Maternal rehospitalization after initial discharge from the hospital assessed by telephone call to mother	7 days
Percentage of neonatal rehospitalization	Neonatal rehospitalization after initial discharge from the hospital assessed by telephone call to mother	7 days
Percentage of neonates with neonatal encephalopathy by Sarnat Score	Documentation of neonatal neurological exam determined by "modified Sarnat Score (no, mild, moderate, and severe"; higher score indicates more encephalopathy	24 hours after birth
Percentage of neonates with neonatal encephalopathy by Thompson Score	Documentation of neonatal neurological exam determined by "Thompson Score (no, mild, moderate, and severe)"; higher score indicates more severe encephalopathy	24 hours after birth

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Health and Medical Research Council, Australia; Lagos State University; University of Lagos, Nigeria; The University of Queensland; Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso; Mater Medical Research Institute
• Investigators: Principal Investigator: Waldemar A Carlo, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: July 22, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Sildenafil citrate
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Asphyxia Neonatorum; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Substandard Drugs; Pharmaceutical Preparations; Dosage Forms; Amides; Purines; Sulfonamides; Sulfones; Piperazines; Sildenafil Citrate; Counterfeit Drugs; Tablets
• Other Study ID Numbers: UAB-300012809; Dixon Endow Chair/3102800 (Other Identifier: University of Alabama at Birmingham)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No