Clinical trial NCT03669185: Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
Official title: Pentaerithrityltetranitrat (PETN) Zur Sekundärprophylaxe Der Intrauterinen Wachstumsretardierung
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Fetal Growth Retardation
Pregnancy Related
Intrauterine Growth Restriction
Keywords: PETN
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
First posted: 2018-09-13
Enrollment: 324
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants who develop intrauterine/fetal growth restriction or perinatal death.
timeFrame: 19 weeks of pregnancy - seventh day of life
Secondary outcomes:
measure: severe morbidity
timeFrame: 19 weeks of pregnancy - seventh day of life
measure: birth weight
timeFrame: 19-40 weeks of pregnancy
measure: Number of participants who developed FGR
timeFrame: 19-40 weeks of pregnancy
measure: admission to NICU
timeFrame: Birth to discharge from the hospital
measure: infant outcome
timeFrame: birth to discharge from NICU
measure: number of premature deliveries
timeFrame: 19 to 37 weeks of gestation
measure: mortality
timeFrame: 19 weeks of pregnancy - seventh day of life
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: Universitäts-Frauenklinik Tübingen
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: München
country: Germany
facility: Städtisches Klinikum München
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Halle
country: Germany
facility: Krankenhaus St. Elisabeth und St. Barbara
state: Sachsen-Anhalt
city: Halle
country: Germany
facility: Universitätsklinik Halle
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: Uniklinikum Leipzig
state: Sachsen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig Holstein
state: Schleswig-Holstein
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Berlin
country: Germany
facility: Berlin Charité Campus Mitte
city: Berlin
country: Germany
facility: Berlin Vivantes Klinikum Neukölln
Study officials:
affiliation: Universital Hospital Jena
name: Tanja Groten, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Groten T, Lehmann T, Schleussner E; PETN Study Group. Does Pentaerytrithyltetranitrate reduce fetal growth restriction in pregnancies complicated by uterine mal-perfusion? Study protocol of the PETN-study: a randomized controlled multicenter-trial. BMC Pregnancy Childbirth. 2019 Sep 14;19(1):336. doi: 10.1186/s12884-019-2456-7.