Trial document




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  DRKS00012418

Trial Description

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Title

Effects of late pregnancy antihypertensive beta-blocker therapy on fetal outcome - An observational cohort study of the Berlin Institute for Clinical Pharmacology and Toxicology

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Trial Acronym

Beta-blockers in late pregnancy

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Hypertension is the most prevalent cardiovascular disease in pregnancy. This study analyses the correlation between maternal treatment with beta-blockers during the 2. and/ or 3. trimester and adverse effects in the newborn, detected after birth. Data analysis will be based on cases which are prospectively ascertained and archived in the pharmacovigilance database of the German Embryotox Pharmacovigilance Centre.

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Brief Summary in Scientific Language

There is evidence that maternal treatment with beta-blockers during the second and third trimester may be correlated with adverse effects in the exposed neonates. The mentioned adverse reactions in particular are neonatal hypoglycemia, neonatal bradycardia, neonatal apnea and small-for-gestational-age. The following beta-blockers will be analyzed: metoprolol and bisoprolol.
Sufficient data on prenatal risk and safety are still lacking. Therefore, it is urgently needed to improve the risk profile of beta-blockers in pregnancy. This would support adequate counselling of pregnant women and their health care providers.
Objectives are to estimate the risk of postnatal complications in newborns after fetal exposure to the study medication during the second and third trimester. This will be estimated compared to a non-exposed control group and compared to a hypertension reference group.
The Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy counsels patients or their physicians about the risk of medication during pregnancy. This counselling mainly takes place in early pregnancy when outcome or prenatal diagnostic is not known. If the pregnant patient agrees, data are recorded by a structured questionnaire. Eight weeks after the estimated date of birth a second questionnaire is sent to collect data about the pregnancy outcome. Analysis of those prospectively ascertained pregnancies can be used for risk assessment of pathologic pregnancy course including postnatal abnormalities. All three groups are recruited from the already collected and archived data.

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Organizational Data

  •   DRKS00012418
  •   2017/05/19
  •   [---]*
  •   yes
  •   Approved
  •   EA4/065/17, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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Health Condition or Problem studied

  •   P05.0 -  Light for gestational age
  •   P70.4 -  Other neonatal hypoglycaemia
  •   P22.8 -  Other respiratory distress of newborn
  •   P07.3 -  Other preterm infants
  •   P95 -  Fetal death of unspecified cause
  •   Q02 -  Microcephaly
  •   10056471 Bradycardia neonatal
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Interventions/Observational Groups

  •   Study group: Treatment with beta-blockers due to hypertension during the 2. and/ or 3. trimester.
    For all three groups the folowing applies:
    Data are recorded prospectively by a structured questionnaire in early pregnancy at the time of first contact. Eight weeks after the estimated date of birth a second questionnaire is sent to collect data about pregnancy outcome.
  •   Healthy control group: No antihypertensive therapy at any time during pregnancy
  •   Hypertension reference group: Treatment with methyldopa due to hypertension during the 2. and/or 3. trimester
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Characteristics

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

Is there an increased rate of the following diagnoses after exposure to the study medication during the 2. and/ or 3. trimester?
a. Neonates which are small-for geatational-age?
b. Neonatal Bradycardia?
c. Neonatal hypoglycaemia
d. Neonatal apnoea?

The Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy counsels patients or their physicians about the risk of medication during pregnancy. This counselling mainly takes place in early pregnancy when outcome or prenatal diagnostic is not known. If the pregnant patient agrees, data are recorded by a structured questionnaire. Eight weeks after the estimated date of birth a further questionnaire is send to collect data about the pregnancy outcome.

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Secondary Outcome

Is there an increased risk for preterm delivery, stillbirth or microcephaly after exposure to the study medication during the 2. and/ or 3. trimester?

The Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy counsels patients or their physicians about the risk of medication during pregnancy. This counselling mainly takes place in early pregnancy when outcome or prenatal diagnostic is not known. If the pregnant patient agrees, data are recorded by a structured questionnaire. Eight weeks after the estimated date of birth a further questionnaire is send to collect data about the pregnancy outcome.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2017/07/01
  •   1092
  •   Monocenter trial
  •   National
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Inclusion Criteria

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

Prospectively ascertained pregnancies

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Exclusion Criteria

Cases with maternal exposure to the following drugs considered as major teratogens: lenalidomide, carbamazepine, methotrexate, mycophenolate, phenobarbital, phenprocoumon, phenytoin, retinoids (acitretin, adapalen, isotretinoin, tazaroten, tretinoin), thalidomide, topiramate, valproic acid, warfarin.
Cases with maternal exposure to the angiotensin-converting-enzyme-inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs).
Women with acute malignancies.

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Addresses

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    • Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité Universitätsmedizin
    • Mr.  Prof. Dr.   Christof  Schaefer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité Universitätsmedizin
    • Ms.  Dr.  Angela  Kayser 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité Universitätsmedizin
    • Ms.  Dr.   Angela  Kayser 
    • 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
    • Kurt-Georg-Kiesinger-Allee 3
    • 53175  Bonn
    • Germany
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    • Bundesministerium für Gesundheit
    • Rochusstr. 1
    • 53123  Bonn
    • Germany
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Status

  •   Enrolling by invitation
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.