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

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ClinicalTrials.gov Identifier: NCT03669185
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
Jena University Hospital

Tracking Information
First Submitted Date  ICMJE August 28, 2018
First Posted Date  ICMJE September 13, 2018
Last Update Posted Date September 13, 2018
Actual Study Start Date  ICMJE July 26, 2017
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
  • 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
  • birth weight [ Time Frame: 19-40 weeks of pregnancy ]
    percentage of children with birth weight below the 3rd, 5th or 10th percentile
  • 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
  • admission to NICU [ Time Frame: Birth to discharge from the hospital ]
    rate of newborns transferred to neonatal intensive care unit
  • infant outcome [ Time Frame: birth to discharge from NICU ]
    rate of newborns with intraventricular cerebral haemorrhage (grade II - IV) or necrotizing enterocolitis, b.o.
  • number of premature deliveries [ Time Frame: 19 to 37 weeks of gestation ]
    number of premature deliveries before completed 34 and 37 weeks of gestation
  • mortality [ Time Frame: 19 weeks of pregnancy - seventh day of life ]
    number of perinatal deaths
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
Official Title  ICMJE Pentaerithrityltetranitrat (PETN) Zur Sekundärprophylaxe Der Intrauterinen Wachstumsretardierung
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Fetal Growth Retardation
  • Pregnancy Related
  • Intrauterine Growth Restriction
Intervention  ICMJE
  • Drug: Pentalong
    Pentalong, 2 x daily 1 tablet, intake max. 133 days
    Other Names:
    • Pentaeritrithyl tetranitrate
    • Pentalong® 50 mg
  • Drug: Placebos
    Placebos, 2 x daily 1 tablet, intake max. 133 days
Study Arms  ICMJE
  • Placebo Comparator: Placebos
    Placebos, 2 times daily 1 tablet, intake max. 133 days
    Intervention: Drug: Placebos
  • Active Comparator: Pentalong
    Pentalong, 2 times daily 1 tablet, intake max. 133 days
    Intervention: Drug: Pentalong
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2018)
324
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2020
Estimated Primary Completion Date July 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: pregnant women between pregnancy week 19+0 and 22+6
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tanja Groten, PD Dr. +49 3641 9 329207 petn@med.uni-jena.de
Contact: Ekkehard Schleußner, Prof. Dr. +49 3641 9 329207 petn@med.uni-jena.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03669185
Other Study ID Numbers  ICMJE ZKS_0021PETN
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jena University Hospital
Study Sponsor  ICMJE Jena University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tanja Groten, PD Dr. Universital Hospital Jena
PRS Account Jena University Hospital
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP