Evaluation of Raltegravir During the Third Trimester of Pregnancy

PREGNANCY Clinical Trial

— ANRS 160 RalFE  

Official title:

Evaluation of the Pharmacokinetic Properties and the Tolerance of Raltegravir During the Third Trimester of Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02099474
• Other study ID #: ANRS 160 RalFE
• Secondary ID: 2013-004571-12
• Status: Completed
• Phase: Phase 2
• First received: March 19, 2014
• Last updated: August 18, 2017
• Start date: June 30, 2014
• Est. completion date: April 2017

Study information

• Verified date: August 2017
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the evolution of raltegravir concentration in the mother (between the 3rd trimester of pregnancy and one month post-delivery) and her neonate, when this drug is used to prevent mother-to-child HIV-1 transmission as part of a combined antiretroviral regimen.

Description:

1. Objectives

1. Principal objective

• To study pharmacokinetic properties of raltegravir in pregnant women infected by HIV-1, during the third trimester of pregnancy (between 30 and 37 weeks of amenorrhea) and 1 month after childbirth (between W4 and W6 postpartum), as well as in their neonate.

2. Secondary objectives

• Estimate the frequency of women receiving raltegravir and having indetectable viral load at delivery (and those having a strictly indetectable viral load, with no signal under the threshold of the technique used).

• Describe the tolerance to raltegravir in pregnant women during the third trimester and in her neonates

2. Methodology

• National multicenter pharmacokinetic study conducted among pregnant women infected by HIV-1 and exposed to raltegravir during pregnancy.

3. Statistical method

• Method of population pharmacokinetic with 5 samples: before the drug intake, 0.5, 3, 8 and 12 hours after the intake at each of the 2 visits (between 30 and 37 weeks of amenorrhea, and 4 to 6 weeks after delivery).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: April 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnant woman, between 30 and 37 weeks of amenorrhea

• 18 years old and over

• Infected by HIV-1

• Receiving a therapeutic combination, stable for at least 15 days before inclusion, with raltegravir at the standard dose (400 mg twice daily) which the doctor plans to maintain till the end of pregnancy and at least one month after delivery

• Informed consent signed by mother and investigator (at the latest day of pre-inclusion and before any examination conducted as part of research)

• Affiliated person or beneficiary of a social security system (medical aid of state or AME is not a social security system)

• Participant agreeing to be registered in the national file of the people who participate in biomedical researches

Exclusion Criteria:

• Infected by HIV-2

• Under 18 years old

• Receiving therapeutic association with atazanavir (Reyataz®), fosamprenavir (Telzir®), or efavirenz ( contained in Sustiva® and Atripla®)

• Currently using medication, drugs or alcohol which can interfere with the research:

rifampicine, phénobarbital, phénytoïne, topical gastrointestinal, antiacid and adsorbents

• Presenting a clinical situation or acute pathology incompatible with the realisation of a pharmacokinetic study.

• Planned absence which could hinder research participation (travel abroad, moving, imminent transfer ...)

• Participating in another research, except the French perinatal survey (ANRS CO1 EPF or ANRS CO11 observatory), including an exclusion period still in progress at the pre-inclusion

• Person under guardianship, or deprived of freedom by a judicial or administrative decision

Related Conditions & MeSH terms

• HIV-1 Infection
• PREGNANCY

Intervention

Other:
• Study of pharmacokinetic properties of raltegravir during the 3rd trimester of pregnancy
Introduction of a catheter for performing 5 blood samples in pregnant women infected by HIV-1, before the raltegravir intake, 0.5, 3, 8 and 12 hours after the intake at each of two visits (between 30 and 37 weeks of amenorrhea, and 4 to 6 weeks after delivery)

Locations

Country	Name	City	State
France	CHU Hôtel Dieu	Paris

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of the AUC and raltegravir trough concentration during and after pregnancy		5 samples: before the drug intake, 0.5, 3, 8 and 12 hours after the intake at each of the 2 visits (between 30 and 37 weeks of amenorrhea, and 4 to 6 weeks after delivery)
Secondary	Estimation of placental transfer of raltegravir	Cmin, Cmax, AUC, t1/2 of raltegravir in newborns.	Up to 72 hours after delivery
Secondary	Study of genetic polymorphism which could modify raltegravir concentrations		Up to 72 hours after delivery
Secondary	Proportion of women having a viral load < 50 cp/mL at delivery		Up to 72 hours after delivery
Secondary	Proportion of maternal-to-child HIV transmission		Up to 72 hours after delivery
Secondary	Untimely stop of raltegravir for toxicity or intolerance		Up to 72 hours after delivery
Secondary	Clinical and biological anomaly occurring during the third trimester of pregnancy and during the first 6 months of life of the neonate.	Number of newborns with adverse events as a measure of safety and tolerability. Newborns will be followed up to 24 weeks of age.	Month 6
Secondary	Estimation of neonatal elimination of raltegravir	Cmin, Cmax, AUC, t1/2 of raltegravir in newborns.	Up to 72 hours after delivery