Clinical trial NCT02099474: Evaluation of Raltegravir During the Third Trimester of Pregnancy
Official title: Evaluation of the Pharmacokinetic Properties and the Tolerance of Raltegravir During the Third Trimester of Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
PREGNANCY
Keywords: HIV-1
HIV mother to child prevention
Raltegravir
Pharmacokinetic
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2014-03-31
Enrollment: 83
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of the AUC and raltegravir trough concentration during and after pregnancy
timeFrame: 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 outcomes:
measure: Estimation of placental transfer of raltegravir
timeFrame: Up to 72 hours after delivery
measure: Study of genetic polymorphism which could modify raltegravir concentrations
timeFrame: Up to 72 hours after delivery
measure: Proportion of women having a viral load < 50 cp/mL at delivery
timeFrame: Up to 72 hours after delivery
measure: Proportion of maternal-to-child HIV transmission
timeFrame: Up to 72 hours after delivery
measure: Untimely stop of raltegravir for toxicity or intolerance
timeFrame: Up to 72 hours after delivery
measure: Clinical and biological anomaly occurring during the third trimester of pregnancy and during the first 6 months of life of the neonate.
timeFrame: Month 6
measure: Estimation of neonatal elimination of raltegravir
timeFrame: Up to 72 hours after delivery
Other outcomes:
Locations:
city: Paris
country: France
facility: CHU Hôtel Dieu
Study officials:
affiliation: CHU Hôtel Dieu PARIS
name: JADE GHOSN, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zheng Y, Hirt D, Delmas S, Lui G, Benaboud S, Lechedanec J, Treluyer JM, Chenevier-Gobeaux C, Arezes E, Gelley A, Amri I, Urien S, Bouazza N, Foissac F, Warszawski J, Ghosn J. Effect of Pregnancy on Unbound Raltegravir Concentrations in the ANRS 160 RalFe Trial. Antimicrob Agents Chemother. 2020 Sep 21;64(10):e00759-20. doi: 10.1128/AAC.00759-20. Print 2020 Sep 21.