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

The University of Alabama at Birmingham

Status and phase: Withdrawn; Phase 3

Conditions: Instrumental Delivery; Affecting Fetus; Neonatal Asphyxia; Intrapartum Fetal Distress; Intrapartum Asphyxia

Treatments: Drug: Placebo Oral Tablet; Drug: Sildenafil 50 mg Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT06522854

UAB-300012809

Dixon Endow Chair/3102800 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: Under 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Oral Sildenafil 50mg

Active Comparator group

Description:

Sildenafil citrate 50mg given orally every eight hours up to 3 doses while mother is in labor

Treatment:

Drug: Sildenafil 50 mg Oral Tablet

Placebo

Placebo Comparator group

Description:

Identical-appearing treatment that does not contain the test drug given orally every eight hours up to 3 doses while mother is in labor

Treatment:

Drug: Placebo Oral Tablet