Instrumental Delivery; Affecting Fetus, Intrapartum Asphyxia, Intrapartum Fetal Distress, Neonatal Asphyxia
Conditions
Keywords
Sildenafil citrate
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.
Interventions
Sildenafil 50 mg given orally every eight hours up to three times while mother is in labor
DRUGPlacebo Oral Tablet
Placebo tablet given orally every eight hours up to three times while mother is in labor
Sponsors
University of Lagos, Nigeria
Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso
Lagos State University
National Health and Medical Research Council, Australia
Mater Medical Research Institute
The University of Queensland
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator and Outcomes Assessor) The only unmasked person will be the pharmacist who dispenses the study medication--sildenafil 50 mg or identical placebo.
Intervention model description
Parallel Assignment 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of operative delivery | 96 hours after enrollment | Documentation of type of delivery |
| Percentage of perinatal mortality | 96 hours after enrollment | Documentation of stillbirth or neonatal death |
| Percentage of use of bag and mask in neonates after delivery | 20 minutes after delivery | Documentation of the use of bag and mask ventilation as resuscitation after delivery |
| Indication for operative delivery | 96 hours after enrollment | Documentation of type of delivery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of mothers who received fetal heart rate monitoring | 96 hours after enrollment | Documentation of rate of heart rate monitoring |
| 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) |
| Percentage of neonates with neonatal encephalopathy by Sarnat Score | 24 hours after birth | Documentation of neonatal neurological exam determined by modified Sarnat Score (no, mild, moderate, and severe; higher score indicates more encephalopathy |
| Percentage of neonates with neonatal encephalopathy by Thompson Score | 24 hours after birth | Documentation of neonatal neurological exam determined by Thompson Score (no, mild, moderate, and severe); higher score indicates more severe encephalopathy |
| Percentage of infants with neonatal hypoxic-ischemic encephalopathy | 96 hours after enrollment | Documentation of neonatal 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 neonatal ICU admissions | 96 hours after enrollment | Documentation of admission to the Neonatal Intensive Care Unit or comparable level of care |
| 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 |
Countries
Nigeria
Outcome results
None listed