NCT02068404

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
75

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Apr 2014

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 18, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 21, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

April 1, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

July 28, 2015

Status Verified

July 1, 2015

Enrollment Period

1.8 years

First QC Date

February 18, 2014

Last Update Submit

July 27, 2015

Conditions

Preterm Labor

Keywords

TocolysisPreterm laborNifedipinePharmacokinetics

Outcome Measures

Primary Outcomes (3)

  • Nifedipine blood concentration

    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

    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

    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 Outcomes (7)

  • Nifedipine side effects (feeling)

    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)

    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)

    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)

    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)

    Evaluation during hospital stay for threatened preterm labour between 20-34 weeks of gestational age (during 30-60 min after nifedipine administration)

  • +2 more secondary outcomes

Study Arms (1)

Nifedipine

OTHER
Drug: Nifedipine

Interventions

NifedipineDRUG
Also known as: Adalat
Nifedipine

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Obstetric Labor, Premature

Interventions

Nifedipine

Condition Hierarchy (Ancestors)

Obstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

DihydropyridinesPyridinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Alice Panchaud, PhD

    Centre Hospitalier Universitaire Vaudois

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Alice Panchaud, PhD

CONTACT

0213144276Alice.Panchaud@chuv.ch

Chantal Csajka, Prof PhD

CONTACT

0213144263Chantal.Csajka@chuv.ch

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Prof PhD

Study Record Dates

First Submitted

February 18, 2014

First Posted

February 21, 2014

Study Start

April 1, 2014

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

July 28, 2015

Record last verified: 2015-07

Locations

CH(1)