Fetal Growth Retardation, Intrauterine Growth Restriction, Pregnancy Related
Conditions
Keywords
PETN
Brief summary
Approximately 10% of all pregnancies experience mal perfusion of the placenta resulting in fetal growth restriction (FGR) of the fetus. FGR is the most important cause of perinatal mortality and morbidity. Impaired placental function determined by insufficient transformation of the uterine arteries and mal-perfusion of the placenta is the leading cause of FGR. So far, there is no treatment option for pregnancies complicated by FGR and the clinical management is restricted to close monitoring, assessing for the optimal time point of delivery of the fetus threatened by intrauterine death. In a pilot study a risk reduction of 38% for the development of severe FGR and FGR or death could be demonstrated by giving the organic nitrate pentaerithrityl-tetranitrate (PETN) to patients recognized at risk for FGR by impaired uterine artery Doppler at mid gestation (Schleussner, 2014). To confirm these results this prospective randomized placebo controlled double-blinded multicentre trial, was initiated.
Detailed description
Affecting approximately 10% of pregnancies, fetal growth restriction (FGR), is the most important cause of perinatal mortality and morbidity. Impaired placental function determined by insufficient transformation of the uterine arteries and mal-perfusion of the placenta is the leading cause of FGR. So far, there is no treatment option for pregnancy complicated by FGR and the clinical management is restricted to close monitoring, assessing for the optimal time point of delivering the fetus threatened by intrauterine death. In a prospective randomized controlled trial a risk reduction of 38% (relative risk RR=0.609, 95% CI 0.367 to 1.011) for the development of IUGR and IUGR or death (RR=0.615, 95% CI 0.378 to 1.000) could be demonstrated by delivering the organic nitrate pentaerithrityl-tetranitrate (PETN) to patients recognized at risk for FGR by impaired uterine artery Doppler at mid gestation (Schleussner, 2014). To confirm these results a prospective randomized placebo controlled double-blinded multicentre trial was now initiated. Eligible patients are pregnant women at risk of developing FGR meeting the inclusion criteria: abnormal uterine artery Doppler ultrasound, defined by a mean PI exceeding 1.6, singleton pregnancy, informed consent and 19+0 to 22+6 weeks of gestation. The composite endpoint of severe FGR (\< birth weight below the 3rd centile) and intrauterine or neonatal death was defined as primary efficacy endpoint. and perinatal death. Key secondary endpoints are development of FGR (defined by birth weight \< 10th percentile), severe FGR (\< birth weight below the 3rd centile), intrauterine or neonatal death, placental abruption and preterm birth.
Interventions
DRUGPentalong
Pentalong, 2 x daily 1 tablet, intake max. 133 days
DRUGPlacebos
Placebos, 2 x daily 1 tablet, intake max. 133 days
Sponsors
Jena University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* abnormal uterine artery Doppler at 19+0 to 22+6 weeks of gestation, defined by a mean pulsatility index (PI) Exceeding 1.6 * singleton pregnancy * age\>/= 18 years * informed consent
Exclusion criteria
* known fetal chromosomal or suspected major structural defects at time of enrollment * premature rupture of membranes at time of enrolment; maternal disease defined as contraindication for intake of PETN * anamnestic known insensitivity to Pentalong® or its ingredients or to medications with similar chemical structure * participation of the patient in another clinical trial (parallel or within the waiting period of a previous clinical trial) * multiple pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who develop intrauterine/fetal growth restriction or perinatal death. | 19 weeks of pregnancy - seventh day of life | Efficiency of PETN to prevent the development of intrauterine/fetal growth restriction or perinatal death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| birth weight | 19-40 weeks of pregnancy | percentage of children with birth weight below the 3rd, 5th or 10th percentile |
| Number of participants who developed FGR | 19-40 weeks of pregnancy | Number of participants who developed FGR, which necessitates delivery before 30 and 34 week of gestation |
| admission to NICU | Birth to discharge from the hospital | rate of newborns transferred to neonatal intensive care unit |
| severe morbidity | 19 weeks of pregnancy - seventh day of life | severe morbidity as a combined result of severe FGR (birth weight below the 3rd or 5th percentile) or perinatal death or premature abruption of placenta |
| number of premature deliveries | 19 to 37 weeks of gestation | number of premature deliveries before completed 34 and 37 weeks of gestation |
| mortality | 19 weeks of pregnancy - seventh day of life | number of perinatal deaths |
| infant outcome | birth to discharge from NICU | rate of newborns with intraventricular cerebral haemorrhage (grade II - IV) or necrotizing enterocolitis, b.o. |
Countries
Germany
Outcome results
None listed