PregnancyNCT02622802
Transplacental Transfer of Drugs Used in Pregnant Women
A study testing paracetamol, Erythromycin and Azithromycin in people with Pregnancy, run by University Hospital, Gasthuisberg at 1 site in Belgium.
Trial summary
The most important guideline for drug prescription concerning pregnant women is 'drugs should be given only if the maternal benefits outweigh the potential risk to the fetus'. However, poor data is available on maternal drug disposition and transfer through the placenta, so the evidence available for decision making… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Pregnancy
- What is being tested?
- paracetamol, Erythromycin and Azithromycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2012to May 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- informed consent has been signed
- (placenta of a) pregnant women with an uncomplicated pregnancy and delivery
Who cannot join
- use of medication during pregnancy
- hypertension, diabetes
- smoking
Trial locations and contacts
1 site in 1 country.
About this study
The most important guideline for drug prescription concerning pregnant women is 'drugs should be given only if the maternal benefits outweigh the potential risk to the fetus'. However, poor data is available on maternal drug disposition and transfer through the placenta, so the evidence available for decision making in clinical practice is weak.
An ex-vivo placenta perfusion model will be used to explore the mechanisms governing differences between fetal and maternal drug exposure. The expression of placental transporters and cytochrome P450 (CYP) enzymes will be investigated in primary placenta cell culture and placental biopsies from different gestational stages to learn how the placental drug transfer and disposition is regulated.
The investigators choose to examine the transfer of paracetamol, erythromycin and azithromycin because these drugs are commonly used in human pregnancies and have different metabolic pathways.
Read the detailed description
- Background While many drugs are administered to pregnant women, only poor data exist to determine a therapeutically optimal and safe drug treatment in this patient population. The general advise on the use of medicines in pregnancy is that you can only prescribe drugs to pregnant women if the benefits for the mother outweigh the risks for the fetus. The problem is that for most medicines safety data are lacking. Most drug effects are dose dependent. So the first step to examine potential fetotoxicity is to test transplacental transfer of drugs. Placental transfer from the maternal to the fetal side occurs primarily via passive diffusion, the physicochemical properties of drugs such as lipid solubility, polarity and molecular weight primarily determine the rate of transfer across the placenta. According to membrane permeability properties, low-molecular-weight, lipid-soluble, unbound and unionized compounds can easily cross the human placenta. In addition, some drugs are pumped across the placenta by various active transporters located on both the fetal and maternal side of the trophoblast layer. The most important transporters are P-glycoprotein (P-gp, encoded by the multidrug resistance (MDR)1 gene), Breast cancer resistance protein (BCRP) and multidrug resistance-associated protein (MRP) 1-3 and 5. The transfer of foreign chemicals across the placenta can also be modified by metabolism in the placenta itself. The human placenta contains multiple enzyme systems, like CYP2E1 and CYP3A4.
- Aim \& methods:
The aim of this study is to determine fetal drug concentrations of paracetamol, erythromycin and azithromycin by transplacental transport in an ex-vivo placenta perfusion model. Simultaneously collected maternal and fetal drug plasma levels will be compared to assess fetal drug levels based on maternal drug plasma levels.
Moreover, the transporter and metabolizing activity of the trophoblast cells will be examined in a primary human trophoblast culture, and expression of enzymes and transporters will be evaluated at different gestational ages in human placenta biopsies.
Medicines: The investigators choose to examine the transfer of paracetamol, erythromycin and azithromycin because these drugs are commonly used in human pregnancies.
Since the ORACLE trial, erythromycin is in Belgium the first choice treatment in patients with preterm rupture of membranes, despite the fact that the pharmacokinetics (PK) of this drug has been hardly studied in pregnant women. Erythromycin is unstable under acidic conditions while azithromycin is a semi-synthetic macrolide, with a better gastro-intestinal tolerability and tissue penetration than erythromycin and an excellent activity against sexually transmitted pathogens, especially Chlamydia trachomatis. Because of these characteristics more physicians start to switch to azithromycin even without PK data available in pregnancy.
Paracetamol (acetaminophen) is used as first choice painkiller in pregnancy, but also for this drug surprisingly few PK data are available.
- Conditions
- Pregnancy
- Being tested
- paracetamol, Erythromycin, Azithromycin
- Keywords
- ex-vivo placenta perfusion, transplacental transfer, paracetamol, erythromycin, azithromycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paracetamolDrug
Also called Paracetamol Sigma Aldrich, acetaminophen
In an ex vivo placenta perfusion study, placental tissue is exposed to paracetamol
ErythromycinDrug
Also called Erythromycin Sigma Aldrich
In an ex vivo placenta perfusion study, placental tissue is exposed to erythromycin
AzithromycinDrug
Also called Azithromycin Sigma Aldrich
In an ex vivo placenta perfusion study, placental tissue is exposed to azithromycin
| Study group | Role | What they receive |
|---|---|---|
| ex-vivo placenta perfusion | Experimental | ex vivo placenta perfusion study with exposure to paracetamol, erythromycin and azithromycin Receives: Drug: paracetamol; Drug: Erythromycin; Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transplacental transfer rate of drugs and their metabolites measured by comparing the concentrations in simultaneously collected samples from the maternal and fetal compartment in a human ex-vivo placenta perfusion model
the drug concentrations will be determined by high performance liquid chromatography and mass spectrometry
Measured: 12 months for each drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2015 (estimated)
- Study startNov 2012
- Primary completionDec 2016
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gasthuisberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristel Van Calsteren, MD PhD, University Hospital, Gasthuisberg
- Investigators
- Kristel Van Calsteren, MD PhD, Principal investigator, University Hospital Gasthuisberg Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02622802
- Sponsor's protocol ID
- PPS201210
- Other IDs
- 2012-004580-51
- Status last verified
- May 2017
- First submitted
- 8 Jun 2015
- Last updated
- 3 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transplacental Transfer of Drugs Used in Pregnant Women
- ClinicalTrials.gov ID
- NCT02622802
- Acronym / sponsor ID
- PPS201210
- Conditions
- Pregnancy
- Keywords
- ex-vivo placenta perfusion, transplacental transfer, paracetamol, erythromycin, azithromycin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- University Hospital, GasthuisbergUniversity, hospital or other
- Study start
- Nov 2012 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 7 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The most important guideline for drug prescription concerning pregnant women is 'drugs should be given only if the maternal benefits outweigh the potential risk to the fetus'. However, poor data is available on maternal drug disposition and transfer through the placenta, so the evidence available for decision making in clinical practice is weak.
An ex-vivo placenta perfusion model will be used to explore the mechanisms governing differences between fetal and maternal drug exposure. The expression of placental transporters and cytochrome P450 (CYP) enzymes will be investigated in primary placenta cell culture and placental biopsies from different gestational stages to learn how the placental drug transfer and disposition is regulated.
The investigators choose to examine the transfer of paracetamol, erythromycin and azithromycin because these drugs are commonly used in human pregnancies and have different metabolic pathways.
Detailed description
- Background While many drugs are administered to pregnant women, only poor data exist to determine a therapeutically optimal and safe drug treatment in this patient population. The general advise on the use of medicines in pregnancy is that you can only prescribe drugs to pregnant women if the benefits for the mother outweigh the risks for the fetus. The problem is that for most medicines safety data are lacking. Most drug effects are dose dependent. So the first step to examine potential fetotoxicity is to test transplacental transfer of drugs. Placental transfer from the maternal to the fetal side occurs primarily via passive diffusion, the physicochemical properties of drugs such as lipid solubility, polarity and molecular weight primarily determine the rate of transfer across the placenta. According to membrane permeability properties, low-molecular-weight, lipid-soluble, unbound and unionized compounds can easily cross the human placenta. In addition, some drugs are pumped across the placenta by various active transporters located on both the fetal and maternal side of the trophoblast layer. The most important transporters are P-glycoprotein (P-gp, encoded by the multidrug resistance (MDR)1 gene), Breast cancer resistance protein (BCRP) and multidrug resistance-associated protein (MRP) 1-3 and 5. The transfer of foreign chemicals across the placenta can also be modified by metabolism in the placenta itself. The human placenta contains multiple enzyme systems, like CYP2E1 and CYP3A4.
- Aim \& methods:
The aim of this study is to determine fetal drug concentrations of paracetamol, erythromycin and azithromycin by transplacental transport in an ex-vivo placenta perfusion model. Simultaneously collected maternal and fetal drug plasma levels will be compared to assess fetal drug levels based on maternal drug plasma levels.
Moreover, the transporter and metabolizing activity of the trophoblast cells will be examined in a primary human trophoblast culture, and expression of enzymes and transporters will be evaluated at different gestational ages in human placenta biopsies.
Medicines: The investigators choose to examine the transfer of paracetamol, erythromycin and azithromycin because these drugs are commonly used in human pregnancies.
Since the ORACLE trial, erythromycin is in Belgium the first choice treatment in patients with preterm rupture of membranes, despite the fact that the pharmacokinetics (PK) of this drug has been hardly studied in pregnant women. Erythromycin is unstable under acidic conditions while azithromycin is a semi-synthetic macrolide, with a better gastro-intestinal tolerability and tissue penetration than erythromycin and an excellent activity against sexually transmitted pathogens, especially Chlamydia trachomatis. Because of these characteristics more physicians start to switch to azithromycin even without PK data available in pregnancy.
Paracetamol (acetaminophen) is used as first choice painkiller in pregnancy, but also for this drug surprisingly few PK data are available.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ex-vivo placenta perfusion | Experimental | Drug: paracetamol, Drug: Erythromycin, Drug: Azithromycinex vivo placenta perfusion study with exposure to paracetamol, erythromycin and azithromycin |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- informed consent has been signed
- (placenta of a) pregnant women with an uncomplicated pregnancy and delivery
Key exclusion criteria (3 listed)
- use of medication during pregnancy
- hypertension, diabetes
- smoking
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| paracetamolAlso: Paracetamol Sigma Aldrich, acetaminophenIn an ex vivo placenta perfusion study, placental tissue is exposed to paracetamol | Drug | ex-vivo placenta perfusion |
| ErythromycinAlso: Erythromycin Sigma AldrichIn an ex vivo placenta perfusion study, placental tissue is exposed to erythromycin | Drug | ex-vivo placenta perfusion |
| AzithromycinAlso: Azithromycin Sigma AldrichIn an ex vivo placenta perfusion study, placental tissue is exposed to azithromycin | Drug | ex-vivo placenta perfusion |
Primary outcome
Transplacental transfer rate of drugs and their metabolites measured by comparing the concentrations in simultaneously collected samples from the maternal and fetal compartment in a human ex-vivo placenta perfusion model
Time frame: 12 months for each drug
the drug concentrations will be determined by high performance liquid chromatography and mass spectrometry
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2017.
Related trials for Pregnancy
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Population Pharmacokinetics of Temocillin in Acute Enterobacterial Pyelonephritis in Children
Pyelonephritis
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
Recruiting
Safety and Performance of UCon Patch Electrode
Urinary Incontinence, Urinary Incontinence, Urge
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristel Van Calsteren, MD PhD principal investigator
University Hospital Gasthuisberg Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing paracetamol, Erythromycin and Azithromycin in people with Pregnancy, run by University Hospital, Gasthuisberg at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transplacental transfer rate of drugs and their metabolites measured by comparing the concentrations in simultaneously collected samples from the maternal and fetal compartment in a human ex-vivo placenta perfusion model (time frame: 12 months for each drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2017.