Trial document




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  DRKS00011568

Trial Description

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Title

Fetotoxicity of NSAIDS and RAAS-inhibitors in the 2nd and 3rd trimester of pregnancy (fetopathy approach)

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Trial Acronym

NSAIDs and RAAS-inhibitors in the 2nd and 3rd trimester of pregnancy

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URL of the Trial

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Brief Summary in Lay Language

It is well-known that medication during pregnancy can harm the unborn child even if exposure takes place after the first trimester. The aim of this study is to examine and specify the risk after maternal intake of the following medications during the fetal period (second and third trimester): Non-steroidal anti-inflammatory/analgesic drugs (NSAIDs), metamizole, angiotensin-converting-enzyme inhibitors (ACE inhibitors) or angiotensin I receptor antagonists (sartans). Two sub-projects will examine, if specific pregnancy complications (fetopathy approach) or renal disorder in children occur more often (pediatric-nephrological approach) after intake of the above mentioned medications during late pregnancy. With the fetopathy approach, pregnant women with the following abnormalities on ultrasound will be examined regarding their medication during pregnancy: premature constriction or closure of ductus arteriosus, oligo- or anhydramnion. With the nephropathy approach, children and adolescents who were seen in the clinic for pediatric nephrology are interviewed with a questionnaire regarding maternal medication intake during pregnancy. Both sub-projects are registered as separate studies, this is the fetopathy approach. For the second sub-project see DRKS00011861.

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Brief Summary in Scientific Language

It is well-known that non-steroidal anti-inflammatory/analgesic drugs (NSAIDs) and RAAS-inhibitors (inhibitors of the renin-anginotensin-aldosetrone-system) can cause fetotoxic effects after exposure during late pregnancy. The aim of this study is to examine and specify the risk after maternal intake of the following medications during the fetal period (second and third) trimester: Non-steroidal anti-inflammatory/analgesic drugs (NSAIDs), metamizole, angiotensin-converting-enzyme inhibitors (ACE inhibitors) or angiotensin I receptor antagonists (sartans).
Maternal intake of NSAIDs can lead through their prostaglandin-inhibiting effect to premature closure of the ductus arteriosus and through inhibition of cox-2 to fetal kidney dysfunction. Possible symptoms of RAAS inhibitor fetopathy are oligohydramnios or anhydramnios, pulmonary hypoplasia, hypocalvaria, joint contractures and neonatal anuria.
To date there are no sufficient data for risk quantification of NSAID/RAAS-inhibitor fetopathy. Further aims of this study are to investigate the sensitive exposure time in which fetotoxic effects might occur and to evaluate if renal diseases might occur in later infancy after prenatal exposure.
In two sub-projects fetotoxic effects of the above mentioned medication will be examined. It is to be investigated after which gestational week an exposure can lead to a constriction of the ductus arteriosus and the development of an oligohydramnios (fetopathy approach). In addition, it is to be examined whether intrauterine exposure to these drugs has long-term effects on the renal function of exposed children or more frequently leads to the development of hypertonus in children and adolescents (pediatric-nephrological approach).
Both sub-projects are registered as separate studies, this is the fetopathy approach. For the second sub-project see
DRKS00011861.

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Organizational Data

  •   DRKS00011568
  •   2017/03/31
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  •   yes
  •   Approved
  •   EA2/116/16, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

  •   DRKS00011861  (DRKS-ID Studienteil Pädiatrisch-nephrologischer Ansatz)
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Health Condition or Problem studied

  •   O41.0 -  Oligohydramnios
  •   P01.2 -  Fetus and newborn affected by oligohydramnios
  •   10049996 Ductus arteriosus premature closure
  •   10013808 Ductus arteriosus stenosis fetal
  •   10050701 Congenital pulmonary hypertension
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Interventions/Observational Groups

  •   Pregnant women with prenatally and/or neonatally confirmed study diagnoses (premature constriction or closure of ductus arteriosus, oligo- or anhydramnion) are examined and evaluated regarding the exposure with certain medications (NSAIDs, metamizole, RAAS-Inhibitoren). Analysis as as case series (pro- or retrospectively) if case number too low.
  •   Confrontation with unremarkable pregnancy courses without study diagnoses (premature constriction or closure of ductus arteriosus, oligo- or anhydramnion) and analysis if enough cases.
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Other
  •   Open (masking not used)
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  •   Other
  •   Prevention
  •   Other
  •   N/A
  •   N/A
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Primary Outcome

1. Can the hypothesis of an fetopathy (oligo- /anhydramnion or premature narrowing/closure of the ductus arteriosus after exposure to certain medications (NSAIDS, metamizole, RAAS-inhibitors) in the 2nd/3rd Trimester be confirmed and if so, can the risk for this be estimated?
2. When in the second half of pregnancy is the sensitive period for fetotoxicity related to the above mentioned medications?
Information regarding this question is collected by means of a questionnaire during and after pregnancy.

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Secondary Outcome

1. Are there any signs of a minimum exposure time and/or a minimum dose before fetopathy develops?
2. Are there any other fetotoxic effects besides the known diagnostic findings of RAAS Inhibitor fetopathy?
Information regarding this question is collected by means of a questionnaire during and after pregnancy.

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Countries of Recruitment

  •   Germany
  •   Switzerland
  •   Italy
  •   Israel
  •   United Kingdom
  •   Netherlands
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2017/11/01
  •   250
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Female
  •   no minimum age
  •   no maximum age
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Additional Inclusion Criteria

Patients with during prenancy confirmed study diagnoses (oligohydramnios, narrowing or premature closure of the ductus arteriosus, pulmonary Hypertension) or the concomitant diseases of the newborn (neonatal or fetal right heart strain).

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Exclusion Criteria

oligohydramnios with premature rupture of membranes

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Addresses

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    • Pharmakovigilanzzentrum Embryonaltoxikologie Charité-Universitätsmedizin
    • Mr.  Prof. Dr. med.  Christof  Schaefer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Pharmakovigilanzzentrum Embryonaltoxikologie Charité-Universitätsmedizin
    • Ms.  Dr. med.  Stefanie  Hultzsch 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Pharmakovigilanzzentrum Embryonaltoxikologie Charité-Universitätsmedizin
    • Ms.  Dr. med.  Stefanie  Hultzsch 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Bundesinstitut für Arzneimittel und Medizinprodukte
    • Georg-Kiesinger-Allee 3
    • 53175  Bonn
    • Germany
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Status

  •   Enrolling by invitation
  •   2018/09/15
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Trial Publications, Results and other Documents

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