Trial document




drksid header

  DRKS00011374

Trial Description

start of 1:1-Block title

Title

Pentaeritrithyl tetranitrate (PETN) for secondary prevention of intrauterine growth restriction

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

PETN Trial

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

https://www.uniklinikum-jena.de/geburtsmedizin/Forschung+_+Wissenschaft/Klinische+Studien/PETN_Studie-p-2196.html

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Approximately 10% of all pregnancies experience mal nutrition of the fetus resulting in intrauterine growth restriction (IUGR). IUGR 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 IUGR. So far, there is no treatment option for pregnancies complicated by IUGR 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 small study at our University Hospital we could demonstrate a risk reduction of 38% for the development of IUGR and IUGR or death by giving the organic nitrate pentaerithrityl-tetranitrate (PETN) to patients recognized at risk for IUGR by impaired uterine artery Doppler at mid gestation (Schleussner, 2014). To confirm these results this bigger study, a prospective randomized placebo controlled double-blinded multicentre trial, was now initiated.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Affecting approximately 10% of pregnancies, intrauterine growth restriction (IUGR), 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 IUGR. So far, there is no treatment option for pregnancy complicated by IUGR 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 we could demonstrate 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) by delivering the organic nitrate pentaerithrityl-tetranitrate (PETN) to patients recognized at risk for IUGR 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 IUGR meeting the inclusion criteria: abnormal uterine artery Doppler ultrasound, defined by a mean PI greater than 1.6, singleton pregnancy, informed consent and 19+0 to 22+6 weeks of gestation. The composite endpoint of severe IUGR (< 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 IUGR (defined by birth weight < 10th percentile), severe IUGR (< birth weight below the 3rd centile), intrauterine or neonatal death, placental abruption and preterm birth.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00011374
  •   2017/06/29
  •   2018/09/14
  •   yes
  •   Approved
  •   5085-02/17, Ethikkommission der Friedrich-Schiller-Universität Jena an der Medizinischen Fakultät
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2016-004396-51 
  •   NCT03669185  (clinicaltrials.gov)
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   10016505: Intrauterine growth retardation
  •   P05 -  Slow fetal growth and fetal malnutrition
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Pentalong® 50 mg (Pentaeritrithyl tetranitrate/PETN), 2 x daily 1 tablet; intake max. 133 days
  •   Placebo, 2 x daily 1 tablet; intake max. 133 days
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Prevention
  •   Parallel
  •   IIIb
  •   Yes
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

This trial investigates the efficacy and safety of PETN to reduce the incidence of intrauterine growth restriction (IUGR), perinatal death and accompanied preterm delivery in women with insufficient placental development and uterine perfusion identified by pathological artery Doppler at 19+0 to 22+6 weeks of gestation.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

1. severe morbidity and mortality as a combined result of severe IUGR (birth weight below the 3rd or 5th percentile) or perinatal death or premature abruption of placenta
2. percentage of children with birth weight below the 3rd, 5th or 10th percentile
3. development of an IUGR, which necessitates delivery before 30 and 34 week of gestation
4. rate of infants who have to be transferred to the intensive care unit in the paediatric clinic
5. rate of infants, who require a breathing, suffer intraventricular cerebral haemorrhage (grade II - IV) or develop necrotizing enterocolitis
6. premature births below accomplished 34 and 37 week of gestation

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2017/08/15
  •   324
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. abnormal uterine artery Doppler at 19+0 to 22+6 weeks of gestation, defined by a mean pulsatility index (PI) greater than 1.6; 2. singleton pregnancy; 3. age>/= 18 years ; 4. informed consent

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Friedrich-Schiller-Universität Jena, vertreten durch Dekan der Medizinischen Fakultät
    • Bachstraße 18
    • 07743  Jena
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universitätsklinikum Jena, Klinik für Geburtsmedizin
    • Ms.  PD Dr. med. habil.  Tanja  Groten 
    • Am Klinikum 1
    • 07747  Jena
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universitätsklinikum Jena, Klinik für Geburtsmedizin
    • Ms.  PD Dr. med. habil.  Tanja  Groten 
    • Am Klinikum 1
    • 07747  Jena
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.