Intrapartum Sildenafil in Laboring Mothers (PRISM)

The University of Alabama at Birmingham

Status and phase: Withdrawn; Phase 3

Conditions: Neonatal Asphyxia; Intrapartum Fetal Distress; Intrapartum Asphyxia; Development, Infant

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06377098

UAB-300010901

UAB Dixon Endowed Ch/3102800 (Other Grant/Funding Number)

Details and patient eligibility

About

The goal of this feasibility pilot clinical trial is to learn if sildenafil citrate 50mg orally, up to three times during labor, can be appropriately administered, with limited clinical side effects, to laboring mothers to determine feasibility across a spectrum of available healthcare resources.

The main questions it aims to answer are:

• What are the fetal heart rate monitoring practices in a low-resource setting?
• What are the indications for operative delivery in a low-resource?
• What is the rate of relevant primary and secondary outcomes to possibly target in a large RCT of intrapartum sildenafil?
• What is the limited effect size of sildenafil citrate on maternal and neonatal outcomes in a low-resource setting?

Researchers will compare the administration of sildenafil citrate 50 mg orally to a placebo (a look-alike substance that contains no drug) to see if procedures are feasible, the drug is tolerated, the target outcomes are achievable, and effect size is as expected.

Participants will:

• Take Sildenafil 50 mg/placebo every eight hours or a placebo every eight hours for up to 24 hours during labor
• Have the (mothers & babies) medical charts reviewed for outcomes, including fetal distress, operative delivery, maternal side effects, neonatal bag & mask ventilation, Apgar scores, and seizures.
• Have a neonatal neurological assessment prior to discharge
• Have phone call assessments for re-hospitalization or mortality 7 days post-delivery
• Receive child development assessments at 1 year, 2 years and 3 years of age by the Ages and Stages Questionnaire administered via a telephone call

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

After informed consent obtained, mother will be randomized, using computer-generated stratified randomization codes by the pharmacy. Clinicians, researcher, and primary caregivers will be masked. Subjects will be randomly assigned to either the treatment arm or the placebo concurrent control.

Eligible women who consent for the study 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. Outcomes will be collected following delivery, discharge, and 7-days post-partum. 7-day follow-up for outcomes will be obtained per a telephone call. One, two, and three year infant developmental and behavior outcome will be assessed using the Ages and Stages Questionnaire.

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 gestation)

   • Early labor will be defined as cervical dilation less than or equal to 6 cm
   • 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 or minors 14-17yrs eligible in countries where married or pregnant minors or their authorized representatives are legally permitted to give consent

4. A single, live fetus in cephalic presentation confirmed prior to randomization

Exclusion criteria

1. Unknown gestational age
2. Maternal history of cesarean delivery
3. Advanced stage of labor (>6 cm or 10 cm cervical dilation per local standards) and pushing, or too distressed to understand, confirm, or give informed consent regardless of cervical dilation
4. Not capable of giving consent due to other health problems, such as obstetric emergencies (i.e. antepartum hemorrhage) or mental disorder
5. Maternal contraindication to sildenafil therapy, such as hypersensitivity to nitrates or nitrites
6. Any medical condition considered a contraindication per the judgement of site investigators
7. Recognized fetal anomaly
8. Any maternal medical condition or status that precludes informed consent
9. Non-emancipated minors (as per local regulations
10. Plan for cesarean delivery prior to enrollment
11. 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