Clinical trial NCT06522854: Oral Sildenafil Citrate to Improve Maternal and Neonatal Outcomes in Low-resource Settings
Official title: Oral Sildenafil Citrate to Improve Maternal and Neonatal Outcomes in Low-resource Settings: A Randomized Pilot Feasibility Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Intrapartum Fetal Distress
Neonatal Asphyxia
Intrapartum Asphyxia
Instrumental Delivery; Affecting Fetus
Keywords: Sildenafil citrate
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: University of Lagos, Nigeria
name: Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso
name: Lagos State University
name: National Health and Medical Research Council, Australia
name: Mater Medical Research Institute
name: The University of Queensland
First posted: 2024-07-26
Enrollment: 2000
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: Parallel Assignment Double blinded, placebo controlled, 1:1 parallel allocation, randomized feasibility trial
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of perinatal mortality
timeFrame: 96 hours after enrollment
measure: Percentage of use of bag and mask in neonates after delivery
timeFrame: 20 minutes after delivery
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 neonates with neonatal encephalopathy by Sarnat Score
timeFrame: 24 hours after birth
measure: Percentage of neonates with neonatal encephalopathy by Thompson Score
timeFrame: 24 hours after birth
measure: Percentage of infants with neonatal hypoxic-ischemic encephalopathy
timeFrame: 96 hours after enrollment
measure: Percentage of neonates with hypoxemia
timeFrame: 48 hours after birth or at discharge, if early discharge
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
Other outcomes:
Locations:
city: Lagos
country: Nigeria
facility: Lagos Island Maternity Hospital
state: Lagos State
city: Lagos
country: Nigeria
facility: University Teaching Hospital, University of Lagos
state: Lagos State
city: Surulere
country: Nigeria
facility: Mother and Child Hospital
state: Lagos State
city: Ogbomoso
country: Nigeria
facility: Ladoke Akintola University of Technology Teaching Hospital
state: Oyo State
Study officials:
affiliation: University of Alabama at Birmingham
name: Waldemar A Carlo, MD
role: PRINCIPAL_INVESTIGATOR
References: