Clinical trial NCT06377098: Intrapartum Sildenafil in Laboring Mothers
Official title: Sildenafil Citrate to Improve Maternal and Neonatal Outcomes in Low-Resource Settings: A Randomized Pilot Feasibility Trial: Pilot Randomized Intrapartum Sildenafil in Mothers
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Neonatal Asphyxia
Intrapartum Fetal Distress
Development, Infant
Intrapartum Asphyxia
Keywords: Sildenafil citrate
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: University Teaching Hospital, Lusaka, Zambia
name: Egerton University
name: Cameroon Baptist Convention Health
First posted: 2024-04-22
Enrollment: 1000
Sex: ALL
Minimum age (years): 0
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded, placebo-controlled, 1:1 parallel allocation, randomized feasibility trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of perinatal mortality
timeFrame: 96 hours after enrollment
measure: Percentage of operative delivery
timeFrame: 96 hours after enrollment
measure: Indication for operative delivery
timeFrame: 96 hours after enrollment
Secondary outcomes:
measure: Percentage of mothers who received fetal heart rate monitoring
timeFrame: 96 hours after enrollment
measure: Indication for fetal heart rate monitoring
timeFrame: 96 hours after enrollment
measure: Apgar Score
timeFrame: 1 minute and 5 minutes after birth
measure: Percentage of use of bag and mask ventilation in neonates
timeFrame: 20 minutes after delivery
measure: Percentage of neonates with neonatal encephalopathy
timeFrame: 24 hours after birth
measure: Percentage of neonates with neonatal encephalopathy
timeFrame: 24 hours after birth
measure: Percentage of neonates with hypoxemia
timeFrame: 48 hours after birth or at discharge, if early discharge
measure: Percentage of infants with neonatal hypoxic-ischemic encephalopathy
timeFrame: 96 hours after enrollment
measure: Percentage of neonatal ICU admissions
timeFrame: 96 hours after enrollment
measure: Percentage of maternal rehospitalization
timeFrame: 7 days
measure: Percentage of neonatal rehospitalization
timeFrame: 7 days
measure: Infant/child developmental assessment
timeFrame: 12 months, 24 months, 36 months
Other outcomes:
Locations:
city: Douala
country: Cameroon
facility: Cameroon Baptist Convention Health Services
city: Nakuru
country: Kenya
facility: Egerton University/Nakuru County Referral Hospital
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: University of Alabama at Birmingham
name: Waldemar A Carlo, MD
role: PRINCIPAL_INVESTIGATOR
References: