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

Pregnancy Related Clinical Trial

— PETN  

Official title:

Pentaerithrityltetranitrat (PETN) Zur Sekundärprophylaxe Der Intrauterinen Wachstumsretardierung

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03669185
• Other study ID #: ZKS_0021PETN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 26, 2017
• Est. completion date: October 31, 2021

Study information

• Verified date: February 2021
• Source: Jena University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 324
• Est. completion date: October 31, 2021
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fetal Growth Retardation
• Intrauterine Growth Restriction
• Pregnancy Related

Intervention

Drug:
• Pentalong
Pentalong, 2 x daily 1 tablet, intake max. 133 days
• Placebos
Placebos, 2 x daily 1 tablet, intake max. 133 days

Locations

Country	Name	City	State
Germany	Berlin Charité Campus Mitte	Berlin
Germany	Berlin Vivantes Klinikum Neukölln	Berlin
Germany	Universitätsklinikum Bonn	Bonn	Nordrhein-Westfalen
Germany	Universitätsklinikum Dresden	Dresden	Sachsen
Germany	Krankenhaus St. Elisabeth und St. Barbara	Halle	Sachsen-Anhalt
Germany	Universitätsklinik Halle	Halle	Sachsen-Anhalt
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinikum Jena	Jena	Thüringen
Germany	Universitätsklinikum Schleswig Holstein	Kiel	Schleswig-Holstein
Germany	Uniklinikum Leipzig	Leipzig	Sachsen
Germany	Klinikum der Universität München	München	Bayern
Germany	Städtisches Klinikum München	München	Bayern
Germany	Universitäts-Frauenklinik Tübingen	Tübingen	Baden-Württemberg
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
Jena University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who develop intrauterine/fetal growth restriction or perinatal death.	Efficiency of PETN to prevent the development of intrauterine/fetal growth restriction or perinatal death.	19 weeks of pregnancy - seventh day of life
Secondary	severe morbidity	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	19 weeks of pregnancy - seventh day of life
Secondary	birth weight	percentage of children with birth weight below the 3rd, 5th or 10th percentile	19-40 weeks of pregnancy
Secondary	Number of participants who developed FGR	Number of participants who developed FGR, which necessitates delivery before 30 and 34 week of gestation	19-40 weeks of pregnancy
Secondary	admission to NICU	rate of newborns transferred to neonatal intensive care unit	Birth to discharge from the hospital
Secondary	infant outcome	rate of newborns with intraventricular cerebral haemorrhage (grade II - IV) or necrotizing enterocolitis, b.o.	birth to discharge from NICU
Secondary	number of premature deliveries	number of premature deliveries before completed 34 and 37 weeks of gestation	19 to 37 weeks of gestation
Secondary	mortality	number of perinatal deaths	19 weeks of pregnancy - seventh day of life

External Links

•   PETN Website
•   Publication Study Protocol