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

• ClinicalTrials.gov Identifier: NCT03669185
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2018
• Last Update Posted: February 25, 2021
• Sponsor: Jena University Hospital
• Information provided by (Responsible Party): Jena University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fetal Growth Retardation; Pregnancy Related; Intrauterine Growth Restriction	Drug: Pentalong; Drug: Placebos	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 324 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Pentaerithrityltetranitrat (PETN) Zur Sekundärprophylaxe Der Intrauterinen Wachstumsretardierung
• Actual Study Start Date: July 26, 2017
• Actual Primary Completion Date: July 31, 2020
• Estimated Study Completion Date: October 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebos; Placebos, 2 times daily 1 tablet, intake max. 133 days	Drug: Placebos; Placebos, 2 x daily 1 tablet, intake max. 133 days
Active Comparator: Pentalong; Pentalong, 2 times daily 1 tablet, intake max. 133 days	Drug: Pentalong; Pentalong, 2 x daily 1 tablet, intake max. 133 days; Other Names: Pentaeritrithyl tetranitrate; Pentalong® 50 mg

Outcome Measures

Primary Outcome Measures :

1. Number of participants who develop intrauterine/fetal growth restriction or perinatal death. [ Time Frame: 19 weeks of pregnancy - seventh day of life ]
   Efficiency of PETN to prevent the development of intrauterine/fetal growth restriction or perinatal death.

Secondary Outcome Measures :

1. severe morbidity [ Time Frame: 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
2. birth weight [ Time Frame: 19-40 weeks of pregnancy ]
   percentage of children with birth weight below the 3rd, 5th or 10th percentile
3. Number of participants who developed FGR [ Time Frame: 19-40 weeks of pregnancy ]
   Number of participants who developed FGR, which necessitates delivery before 30 and 34 week of gestation
4. admission to NICU [ Time Frame: Birth to discharge from the hospital ]
   rate of newborns transferred to neonatal intensive care unit
5. infant outcome [ Time Frame: birth to discharge from NICU ]
   rate of newborns with intraventricular cerebral haemorrhage (grade II - IV) or necrotizing enterocolitis, b.o.
6. number of premature deliveries [ Time Frame: 19 to 37 weeks of gestation ]
   number of premature deliveries before completed 34 and 37 weeks of gestation
7. mortality [ Time Frame: 19 weeks of pregnancy - seventh day of life ]
   number of perinatal deaths

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: pregnant women between pregnancy week 19+0 and 22+6
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

Universitäts-Frauenklinik Tübingen

Tübingen, Baden-Württemberg, Germany, 72076

Universitätsklinikum Ulm

Ulm, Baden-Württemberg, Germany, 89075

Klinikum der Universität München

München, Bayern, Germany, 81377

Städtisches Klinikum München

München, Bayern, Germany, 81545

Medizinische Hochschule Hannover

Hannover, Niedersachsen, Germany, 30625

Universitätsklinikum Bonn

Bonn, Nordrhein-Westfalen, Germany, 53127

Krankenhaus St. Elisabeth und St. Barbara

Halle, Sachsen-Anhalt, Germany, 06110

Universitätsklinik Halle

Halle, Sachsen-Anhalt, Germany, 06120

Universitätsklinikum Dresden

Dresden, Sachsen, Germany, 01307

Uniklinikum Leipzig

Leipzig, Sachsen, Germany, 04103

Universitätsklinikum Schleswig Holstein

Kiel, Schleswig-Holstein, Germany, 24105

Universitätsklinikum Jena

Jena, Thüringen, Germany, 07747

Berlin Charité Campus Mitte

Berlin, Germany, 10117

Berlin Vivantes Klinikum Neukölln

Berlin, Germany, 12351

Sponsors and Collaborators

Jena University Hospital

Investigators

• Principal Investigator: Tanja Groten, PD Dr.; Universital Hospital Jena

More Information

Additional Information:

PETN Website 

Publication Study Protocol 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jena University Hospital
• ClinicalTrials.gov Identifier: NCT03669185
• Other Study ID Numbers: ZKS_0021PETN
• First Posted: September 13, 2018
• Last Update Posted: February 25, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jena University Hospital:

PETN

Additional relevant MeSH terms:

Fetal Growth Retardation; Fetal Diseases; Pregnancy Complications; Growth Disorders; Pathologic Processes