Nifedipine Pharmacokinetics and Pharmacodynamics When Used as a Tocolytic in Acute Threatened Preterm Labour

July 27, 2015 updated by: Chantal Csajka

Nifedipine Pharmacokinetics and Pharmacodynamics When Used as a Tocolytic in Patients Hospitalized for Acute Threatened Preterm Labour

Preterm birth is the leading cause of perinatal mortality and morbidity. According to WHO, 15 million children are born prematurely (gestational age < 37 weeks) in the world each year while 7% of them die because of complications associated with prematurity. Despite constant improvement of obstetrical care, the number of preterm births has increased over the last decades and prematurity is still the most frequent cause of prenatal hospitalization in industrialized countries.

The American College of Obstetricians and Gynecologists as well as the Royal College of Obstetricians and Gynaecologists recommend nifedipine as a first-line tocolytic in case of acute threatened preterm labour. Clinical experience show however an important variability in treatment response among pregnant women. In spite of its large use in obstetrics as a tocolytic agent, nifedipine is prescribed off-label. As a consequence no international consensus on optimal dose schedule has so far been proposed.

Small sample size and heterogeneousness of tocolysis administration protocols make it difficult to compare the little data available on the pharmacokinetics of nifedipine in pregnant women. Nevertheless an important interindividual variability in concentrations has been identified (CV=12-76%) but very few studies have investigated the possible reasons of this variability in pregnant women. Genetic and environmental factors involved in drug distribution and metabolism (e.g. enzymatic activity, CYP 3A5 genotype) might partially explain variability in drug levels and therefore differences in treatment response.

The goal of this study is to quantify the variability in nifedipine pharmacokinetics and identify potential genetic and non-genetic sources of variability in nifedipine pharmacokinetics in pregnant women. The relationship between concentration and treatment response will be evaluated and will serve to propose optimal dosage regimen to improve efficacy and reduce side effects associated with this treatment.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

75

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois
        • Contact:
        • Principal Investigator:
          • Alice Panchaud, PhD
        • Sub-Investigator:
          • David Baud, MD PhD MER
        • Sub-Investigator:
          • Chantal Csajka, Prof PhD
        • Sub-Investigator:
          • Chin B Eap, Prof PhD
        • Sub-Investigator:
          • Karine Lepigeon
        • Sub-Investigator:
          • Etienne Weisskopf, PharmD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women under nifedipine treatment for acute threatened preterm labour
  • Hospitalization for this condition in the maternity of the University Hospital of Lausanne (CHUV)
  • Gestational age of 20-34 weeks
  • Signed informed consent

Exclusion Criteria:

  • Patient < 18 years
  • Contraindication to tocolysis for clinical reasons (e.g. severe pre-eclampsia, chorioamnionitis, placental anomaly, letal fetal anomaly, important intrauterine growth restriction) or current labour
  • Contraindication to nifedipine
  • Severe renal or hepatic impairment
  • Fever > 37.5°C
  • Incapacity of communication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Nifedipine
Drug: Nifedipine
Other Names:
  • Adalat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nifedipine blood concentration
Time Frame: Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with routine blood sampling)
In total, 3 blood samples are collected after nifedipine administration during hospitalization at the same moment as routine blood sampling. Therefore collection hours are not specified.
Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with routine blood sampling)
Genotyping
Time Frame: Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with nifedipine blood sampling)
Pharmacogenetic analysis of genes involved in drug distribution, metabolism and action (e.g. CYP 3A5, POR, CACNA1C) are performed on blood cells of one nifedipine blood sample taken during hospitalization.
Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with nifedipine blood sampling)
Phenotyping
Time Frame: Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with routine blood sampling)
Phenotyping of CYP 3A activity is performed during hospitalization by midazolam administration as a probe. Blood is taken at the same moment as routine blood sampling. Therefore collection hour is not specified.
Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with routine blood sampling)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nifedipine side effects (feeling)
Time Frame: Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (at 1-3 h after nifedipine administration)
Nifedipine side effects are collected by questioning patients during hospitalization approximately at 1-3 h after nifedipine administration to assess security of tocolysis (e.g. headache, erythema, nausea).
Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (at 1-3 h after nifedipine administration)
Maternal heart rate (measurement)
Time Frame: Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (at 1-3 h after nifedipine administration)
Maternal heart rate is measured by blood pressure meter during hospitalization approximately at 1-3 h after nifedipine administration to assess security of tocolysis.
Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (at 1-3 h after nifedipine administration)
Maternal blood pressure (measurement)
Time Frame: Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (at 1-3 h after nifedipine administration)
Maternal blood pressure is measured by blood pressure meter during hospitalization approximately at 1-3 h after nifedipine administration to assess security of tocolysis.
Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (at 1-3 h after nifedipine administration)
Fetal heart rate (measurement)
Time Frame: Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 30-60 min after nifedipine administration)
Fetal heart rate is measured by cardiotocography during hospitalization approximately during 30-60 min after nifedipine administration to assess security of tocolysis.
Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 30-60 min after nifedipine administration)
Uterine contraction (measurement)
Time Frame: Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 30-60 min after nifedipine administration)
Uterine contraction is measured by cardiotocography during hospitalization approximately during 30-60 min after nifedipine administration to assess efficacy of tocolysis.
Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 30-60 min after nifedipine administration)
Uterine contraction (feeling)
Time Frame: Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 2 h after nifedipine administration)
Frequency and intensity of uterine contraction are collected by questioning patients during hospitalization approximately during 2 h after nifedipine administration to assess efficacy of tocolysis.
Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 2 h after nifedipine administration)
Birth date
Time Frame: Data collection after hospital stay for threatened preterm labour between 20-34 weeks of gestational age (potentially at 20-41 weeks of gestational age)
Time between hospitalization for acute threatened preterm labour and effective birth date is calculated to assess efficacy of tocolysis. This time can be extremely short (inefficacy of tocolysis and delivery in next few hours/days) or correspond to full term.
Data collection after hospital stay for threatened preterm labour between 20-34 weeks of gestational age (potentially at 20-41 weeks of gestational age)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chantal Csajka

Investigators

  • Principal Investigator: Alice Panchaud, PhD, Centre Hospitalier Universitaire Vaudois

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Anticipated)

January 1, 2016

Study Completion (Anticipated)

January 1, 2016

Study Registration Dates

First Submitted

February 18, 2014

First Submitted That Met QC Criteria

February 19, 2014

First Posted (Estimate)

February 21, 2014

Study Record Updates

Last Update Posted (Estimate)

July 28, 2015

Last Update Submitted That Met QC Criteria

July 27, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PK/PD_Nifedipine

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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