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

Preterm Labor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02068404
• Other study ID #: PK/PD_Nifedipine
• Status: Recruiting
• Phase: Phase 4
• First received: February 18, 2014
• Last updated: July 27, 2015
• Start date: April 2014
• Est. completion date: January 2016

Study information

• Verified date: July 2015
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: Alice Panchaud, PhD
• Phone: 0213144276
• Email: Alice.Panchaud[@]chuv.ch
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Obstetric Labor, Premature
• Premature Birth
• Preterm Labor

Intervention

Drug:
• Nifedipine

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud

Sponsors (1)

Lead Sponsor	Collaborator
Chantal Csajka

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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)	No
Secondary	Nifedipine side effects (feeling)	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)	Yes
Secondary	Maternal heart rate (measurement)	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)	Yes
Secondary	Maternal blood pressure (measurement)	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)	Yes
Secondary	Fetal heart rate (measurement)	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)	Yes
Secondary	Uterine contraction (measurement)	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)	No
Secondary	Uterine contraction (feeling)	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)	No
Secondary	Birth date	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)	No