Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction

Jena University Hospital

Status and phase

Unknown

Phase 3

Conditions

Fetal Growth Retardation

Intrauterine Growth Restriction

Pregnancy Related

Treatments

Drug: Placebos

Drug: Pentalong

Study type

Interventional

Funder types

Other

Identifiers

NCT03669185

ZKS_0021PETN

Details and patient eligibility

About

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.

Full 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.

Enrollment

324 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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