Development, Infant, Intrapartum Asphyxia, Intrapartum Fetal Distress, Neonatal Asphyxia
Conditions
Keywords
Sildenafil citrate
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.
Interventions
Sildenafil 50 mg given orally every eight hours up to three times while mother is in labor
DRUGPlacebo Oral Tablet
Placebo table given orally every eight hours up to three times while mother is in labor
Sponsors
University Teaching Hospital, Lusaka, Zambia
Egerton University
Cameroon Baptist Convention Health
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The only person who will be unmasked will be the pharmacist who will dispense the study medication--either sildenafil 50mg or identical placebo
Intervention model description
Double blinded, placebo-controlled, 1:1 parallel allocation, randomized feasibility trial
Eligibility
Sex/Gender
ALL
Age
0 Days to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of perinatal mortality | 96 hours after enrollment | Documentation of stillbirth or neonatal death |
| Percentage of operative delivery | 96 hours after enrollment | Documentation of type of delivery |
| Indication for operative delivery | 96 hours after enrollment | Documentation of type of delivery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of use of bag and mask ventilation in neonates | 20 minutes after delivery | Documentation of the use of bag and mask ventilation as resuscitation after delivery |
| Percentage of neonates with neonatal encephalopathy | 24 hours after birth | Documentation of neonatal neurological exam determined by modified Sarnat Score (no, mild, moderate, and severe) ; higher score indicates more severe encephalopathy |
| Percentage of neonates with hypoxemia | 48 hours after birth or at discharge, if early discharge | Documentation of saturations \< 95% measured by noninvasive pre/post pulse oximetry |
| Percentage of infants with neonatal hypoxic-ischemic encephalopathy | 96 hours after enrollment | Documentation of neonatal encephalopathy |
| Percentage of mothers who received fetal heart rate monitoring | 96 hours after enrollment | Documentation of rate of heart rate monitoring |
| Percentage of maternal rehospitalization | 7 days | Maternal rehospitalization after initial discharge from the hospital assessed by telephone call to mother |
| Percentage of neonatal rehospitalization | 7 days | Neonatal rehospitalization after initial discharge from the hospital assessed by telephone call to mother |
| Infant/child developmental assessment | 12 months, 24 months, 36 months | 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) |
| Percentage of neonatal ICU admissions | 96 hours after enrollment | Documentation of admission to the Neonatal Intensive Care Unit or comparable level of care |
| Indication for fetal heart rate monitoring | 96 hours after enrollment | Documentation of the indication for use of fetal heart rate monitoring |
| Apgar Score | 1 minute and 5 minutes after birth | Documentation of Apgar score at 1 minute and 5 minutes (Value 0-10, with 10 meaning better outcome) |
Countries
Cameroon, Kenya, Zambia
Outcome results
None listed