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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Centre Hospitalier Universitaire Vaudois
Sponsor:
Information provided by (Responsible Party):
Chantal Csajka, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT02068404
First received: February 18, 2014
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Preterm Labor
Drug: Nifedipine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nifedipine Pharmacokinetics and Pharmacodynamics When Used as a Tocolytic in Patients Hospitalized for Acute Threatened Preterm Labour

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • Genotyping [ Time Frame: Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with nifedipine blood sampling) ] [ Designated as safety issue: No ]
    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.

  • Phenotyping [ Time Frame: Blood collection during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (together with routine blood sampling) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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).

  • 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) ] [ Designated as safety issue: Yes ]
    Maternal heart rate is measured by blood pressure meter during hospitalization approximately at 1-3 h after nifedipine administration to assess security of tocolysis.

  • 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) ] [ Designated as safety issue: Yes ]
    Maternal blood pressure is measured by blood pressure meter during hospitalization approximately at 1-3 h after nifedipine administration to assess security of tocolysis.

  • 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) ] [ Designated as safety issue: Yes ]
    Fetal heart rate is measured by cardiotocography during hospitalization approximately during 30-60 min after nifedipine administration to assess security of tocolysis.

  • 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) ] [ Designated as safety issue: No ]
    Uterine contraction is measured by cardiotocography during hospitalization approximately during 30-60 min after nifedipine administration to assess efficacy of tocolysis.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 75
Study Start Date: March 2014
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Nifedipine Drug: Nifedipine
Other Name: Adalat

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02068404

Contacts
Contact: Alice Panchaud, PhD 0213144276 ext +41 Alice.Panchaud@chuv.ch
Contact: Chantal Csajka, Prof PhD 0213144263 ext +41 Chantal.Csajka@chuv.ch

Locations
Switzerland
Centre Hospitalier Universitaire Vaudois Not yet recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Alice Panchaud, PhD    0213144276 ext +41    Alice.Panchaud@chuv.ch   
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         
Sponsors and Collaborators
Chantal Csajka
Investigators
Principal Investigator: Alice Panchaud, PhD Centre Hospitalier Universitaire Vaudois
  More Information

No publications provided

Responsible Party: Chantal Csajka, Prof PhD, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT02068404     History of Changes
Other Study ID Numbers: PK/PD_Nifedipine
Study First Received: February 18, 2014
Last Updated: February 19, 2014
Health Authority: Switzerland: Ethikkommission

Keywords provided by Centre Hospitalier Universitaire Vaudois:
Tocolysis
Preterm labor
Nifedipine
Pharmacokinetics

Additional relevant MeSH terms:
Obstetric Labor Complications
Obstetric Labor, Premature
Pregnancy Complications
Nifedipine
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014