Intrapartum Sildenafil in Laboring Mothers

Development, Infant Clinical Trial

— PRISM  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06377098
• Other study ID #: UAB-300010901
• Secondary ID: UAB Dixon Endowe
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 1, 2024
• Est. completion date: January 31, 2028

Study information

• Verified date: June 2024
• Source: University of Alabama at Birmingham
• Contact: Waldemar A Carlo, MD
• Phone: 205 934-4680
• Email: wacarlo[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1000
• Est. completion date: January 31, 2028
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Development, Infant
• Fetal Distress
• Neonatal Asphyxia

Intervention

Drug:
• Sildenafil 50 mg Oral Tablet
Sildenafil 50 mg given orally every eight hours up to three times while mother is in labor
• Placebo Oral Tablet
Placebo table given orally every eight hours up to three times while mother is in labor

Locations

Country	Name	City	State
Cameroon	Cameroon Baptist Convention Health Services	Douala
Kenya	Egerton University/Nakuru County Referral Hospital	Nakuru
Zambia	University Teaching Hospital	Lusaka

Sponsors (4)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Cameroon Baptist Convention Health, Egerton University, University Teaching Hospital, Lusaka, Zambia

Countries where clinical trial is conducted

Cameroon,  Kenya,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of perinatal mortality	Documentation of stillbirth or neonatal death	96 hours after enrollment
Primary	Percentage of operative delivery	Documentation of type of delivery	96 hours after enrollment
Primary	Indication for operative delivery	Documentation of type of delivery	96 hours after enrollment
Secondary	Percentage of mothers who received fetal heart rate monitoring	Documentation of rate of heart rate monitoring	96 hours after enrollment
Secondary	Indication for fetal heart rate monitoring	Documentation of the indication for use of fetal heart rate monitoring	96 hours after enrollment
Secondary	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
Secondary	Percentage of use of bag and mask ventilation in neonates	Documentation of the use of bag and mask ventilation as resuscitation after delivery	20 minutes after delivery
Secondary	Percentage of neonates with neonatal encephalopathy	Documentation of neonatal neurological exam determined by "modified Sarnat Score (no, mild, moderate, and severe)" ; higher score indicates more severe encephalopathy	24 hours after birth
Secondary	Percentage of neonates with neonatal encephalopathy	Documentation of neonatal neurological exam determined by "Thompson Score (no, mild, moderate and severe)"; higher score indicates more severe encephalopathy	24 hours after birth
Secondary	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
Secondary	Percentage of infants with neonatal hypoxic-ischemic encephalopathy	Documentation of neonatal encephalopathy	96 hours after enrollment
Secondary	Percentage of neonatal ICU admissions	Documentation of admission to the Neonatal Intensive Care Unit or comparable level of care	96 hours after enrollment
Secondary	Percentage of maternal rehospitalization	Maternal rehospitalization after initial discharge from the hospital assessed by telephone call to mother	7 days
Secondary	Percentage of neonatal rehospitalization	Neonatal rehospitalization after initial discharge from the hospital assessed by telephone call to mother	7 days
Secondary	Infant/child developmental assessment	Score on "Ages and Stages Questionnaire" obtained by telephone call to parent (developmental assessment tool which scores items (Yes=10, Sometimes=5, Not Yet=0) in areas of Communication, Gross Motor, Fine Motor, Problem Solving, and Personal-Social. Scoring of items are totaled and placed on a graph indicating cutoff score. If score is above cutoff, the child's development appears to be on schedule; near the cutoff, may provide learning activities and monitor; and below cutoff, requiring further assessment. 12-month cutoffs (Communication 15.64; Gross Motor 21.49; Fine Motor 34.50; Problem Solving 27.32 and Personal-Social 21.73); 24-month cutoffs ((Communication 25.17; Gross Motor 38.07; Fine Motor 35.16; Problem Solving 29.78 and Personal-Social 31.54); and 36-month cutoffs (Communication 30.99; Gross Motor 36.99; Fine Motor 18.07; Problem Solving 30.29 and Personal-Social 35.33)	12 months, 24 months, 36 months