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

NCT ID: NCT02068404

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-01-31

Brief Summary

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.

Conditions

Preterm Labor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nifedipine

Group Type: OTHER

Nifedipine

Intervention Type: DRUG

Interventions

Nifedipine

Intervention Type: DRUG

Other Intervention Names

Adalat

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chantal Csajka

OTHER

Sponsor Role: lead

Responsible Party

Chantal Csajka

Prof PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alice Panchaud, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudois

Locations

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Alice Panchaud, PhD

Role: CONTACT

Alice.Panchaud@chuv.ch

0213144276 ext. +41

Chantal Csajka, Prof PhD

Role: CONTACT

Chantal.Csajka@chuv.ch

0213144263 ext. +41

Facility Contacts

Alice Panchaud, PhD

Role: primary

Alice.Panchaud@chuv.ch

0213144276 ext. +41

Other Identifiers

PK/PD_Nifedipine

Identifier Type: -

Identifier Source: org_study_id