Effects of late pregnancy antihypertensive beta-blocker therapy on fetal outcome - An observational cohort study of the Berlin Institute for Clinical Pharmacology and Toxicology
Organizational Data
- DRKS-ID:
- DRKS00012418
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2017-05-19
- Last update in DRKS:
- 2019-10-14
- Registration type:
- Prospective
Acronym/abbreviation of the study
Beta-blockers in late pregnancy
URL of the study
No Entry
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.
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.
Health condition or problem studied
- ICD10:
- P05.0 - Light for gestational age
- ICD10:
- P70.4 - Other neonatal hypoglycaemia
- ICD10:
- P22.8 - Other respiratory distress of newborn
- ICD10:
- P07.3 - Other preterm infants
- ICD10:
- P95 - Fetal death of unspecified cause
- ICD10:
- Q02 - Microcephaly
- Free text:
- MedDRA - 10056471 Bradycardia neonatal
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- 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.
- Arm 2:
- Healthy control group: No antihypertensive therapy at any time during pregnancy
- Arm 3:
- Hypertension reference group: Treatment with methyldopa due to hypertension during the 2. and/or 3. trimester
Endpoints
- 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.
- 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.
Study Design
- Purpose:
- Prevention
- Retrospective/prospective:
- No Entry
- Study type:
- Non-interventional
- Longitudinal/cross-sectional:
- No Entry
- Study type non-interventional:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Berlin
Recruitment period and number of participants
- Planned study start date:
- 2017-06-01
- Actual study start date:
- 2017-07-01
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2019-03-26
- Target Sample Size:
- 1092
- Final Sample Size:
- 1107
Inclusion Criteria
- Sex:
- Female
- Minimum Age:
- no minimum age
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- Prospectively ascertained pregnancies
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.
Addresses
Primary Sponsor
- Address:
- Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité UniversitätsmedizinProf. Dr. Christof SchaeferAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49 30 450525702
- Fax:
- +49 30 450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.charite.de
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité UniversitätsmedizinDr. Angela KayserAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49 30 450525702
- Fax:
- +49 30 450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.charite.de
Contact for Public Queries
- Address:
- Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité UniversitätsmedizinDr. Angela KayserAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49 30 450525702
- Fax:
- +49 30 450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.charite.de
Principal Investigator
- Address:
- Pharmakovigilanz- und Beratungszentrum Embryonaltoxikologie Charité UniversitätsmedizinDr. Angela KayserAugustenburger Platz 113353 BerlinGermany
- Telephone:
- +49 30 450525702
- Fax:
- +49 30 450525902
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.charite.de
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesministerium für GesundheitRochusstr. 153123 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bundesgesundheitsministerium.de
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Bundesinstitut für Arzneimittel und MedizinprodukteKurt-Georg-Kiesinger-Allee 353175 BonnGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.bfarm.de/cln_103/DE/Home/home_node.html
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Charité – Universitätsmedizin BerlinCharitéplatz 110117 BerlinGermany
- Telephone:
- (+49)30-450517222
- Fax:
- (+49)30-450517952
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2017-04-05
- Ethics committee number:
- EA4/065/17
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2017-04-26
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No Entry
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- Original Article, Kayser et al, Journal of Hypertension, Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry