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

NCT ID: NCT03669185

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 324 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-26
• Study Completion Date: 2021-10-31

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.

Conditions

Fetal Growth Retardation; Pregnancy Related; Intrauterine Growth Restriction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Placebos

Placebos, 2 times daily 1 tablet, intake max. 133 days

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Placebos, 2 x daily 1 tablet, intake max. 133 days

Pentalong

Pentalong, 2 times daily 1 tablet, intake max. 133 days

Group Type: ACTIVE_COMPARATOR

Pentalong

Intervention Type: DRUG

Pentalong, 2 x daily 1 tablet, intake max. 133 days

Interventions

Pentalong

Pentalong, 2 x daily 1 tablet, intake max. 133 days

Intervention Type: DRUG

Placebos

Placebos, 2 x daily 1 tablet, intake max. 133 days

Intervention Type: DRUG

Other Intervention Names

Pentaeritrithyl tetranitrate; Pentalong® 50 mg

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Jena University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tanja Groten, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

Universital Hospital Jena

Locations

Universitäts-Frauenklinik Tübingen

Tübingen, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Klinikum der Universität München

München, Bavaria, Germany

Städtisches Klinikum München

München, Bavaria, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, Germany

Universitätsklinikum Dresden

Dresden, Saxony, Germany

Uniklinikum Leipzig

Leipzig, Saxony, Germany

Krankenhaus St. Elisabeth und St. Barbara

Halle, Saxony-Anhalt, Germany

Universitätsklinik Halle

Halle, Saxony-Anhalt, Germany

Universitätsklinikum Schleswig Holstein

Kiel, Schleswig-Holstein, Germany

Universitätsklinikum Jena

Jena, Thuringia, Germany

Berlin Charité Campus Mitte

Berlin, , Germany

Berlin Vivantes Klinikum Neukölln

Berlin, , Germany

Countries

Germany

References

Groten T, Lehmann T, Stadtler M, Komar M, Winkler JL, Condic M, Strizek B, Seeger S, Jager Y, Pecks U, Eckmann-Scholz C, Kagan KO, Hoopmann M, von Kaisenberg CS, Hertel B, Tauscher A, Schrey-Petersen S, Friebe-Hoffmann U, Lato K, Hubener C, Delius M, Verlohren S, Sroka D, Schlembach D, de Vries L, Kraft K, Seliger G, Schleussner E; PETN study group. Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion-12-months follow-up and safety data of the double-blind randomized PETN trial. Am J Obstet Gynecol MFM. 2024 Apr;6(4):101332. doi: 10.1016/j.ajogmf.2024.101332. Epub 2024 Mar 7.

Reference Type: DERIVED

PMID: 38460823 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31521118 (View on PubMed)

Related Links

https://www.uniklinikum-jena.de/geburtsmedizin/petn.html

PETN Website

https://europepmc.org/article/PMC/PMC6744635

Publication Study Protocol

Other Identifiers

ZKS_0021PETN

Identifier Type: -

Identifier Source: org_study_id