Ignite Creation Date:
2025-12-25 @ 3:57 AM
Ignite Modification Date:
2026-02-26 @ 4:19 PM
Study NCT ID:
NCT02738502
Status:
COMPLETED
Last Update Posted:
2021-08-06
First Post:
2016-03-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Prevention of Perinatal Transmission of HIV-1 Without Nucleoside Reverse Transcriptase Inhibitors
Sponsor:
ANRS, Emerging Infectious Diseases
Organization:
Study Overview
Official Title:
An Open-label Phase II Pilot Study of Prevention of Perinatal Transmission of HIV-1 Without Nucleoside Reverse Transcriptase Inhibitors
Status:
COMPLETED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MONOGEST
Brief Summary:
The overall goal is to study the feasibility of darunavir/ritonavir (DRV/r) monotherapy as treatment simplification (switch) in pretreated pregnant women, associated with neonatal prophylaxis with nevirapine, constituting a PMTCT strategy without any Nucleoside Reverse Transcriptase Inhibitor (NRTIs) .
Detailed Description:
90 participants will be enrolled and switch to darunavir monotherapy early in pregnancy (before 16 weeks of amenorrhea) in order to reduce exposure to the antiretroviral nucleos(t)ide analogues. The study treatment during the pregnancy is: darunavir 600 mg + ritonavir 100 mg 2 times 24 (DRV/r) monotherapy This regimen will be started after checking the tolerance of DRV/r 600 mg/100 mg twice daily (recommended dosage for pregnancy in French national recommendations) to replace whatever prior antiretrovirals (ARVs) were used, while maintaining the NRTI backbone for 2 weeks. Woman already receiving a triple drug combination with DRV/r will proceed directly to treatment simplification. If clinical tolerance of DRV/r is satisfactory after 2 weeks, nucleos(t)ides will be stopped. In case of intolerance, the treatment will be determined by the investigator but follow-up of the patient will continue.
No zidovudine will be administered at delivery in case of virological control, according to French Guidelines (Morlat Report 2015).
After delivery, the choice of maternal antiretrovial therapy (ART) is left to the discretion of the clinician and patient.
The mothers are followed up monthly until delivery and the last visit is planes at W4-W6 postpartum. Virological efficacy and safety will be assessed monthly.
In neonates, the prophylactic treatment, nevirapine oral solution, will be administrated as soon as possible in the first 12 hours of life and then for 14 days, once a day at a daily dose of 15 mg for a birthweight ≥ 2.5 kg ; 10 mg for a birthweight ≥ 2 kg and \< 2.5 kg and 2 mg / kg for a birthweight \< 2 kg (WHO Guidelines 2013 - French Guidelines, "Morlat Report" 2015).
Clinical and virological monitoring will be performed at Day 3, Day 15 in case of hospitalization, M1, M3 and M6.
Statistical Methods The analysis of the primary endpoint is the proportion of virological success (VL \< 50 copies/mL at delivery among women remaining on DRV/r). All changes in antiretroviral therapy because of VL ≥ 50 copies/ml will be considered as failures. Women who change antiretroviral therapy for other reasons and/or when pregnancy outcome is before 22 weeks of amenorrhea and \< 500g (non-viable pregnancy according to WHO) will be removed from the denominator.
Analysis of treatment changes, tolerance for the mother and child and factors associated with virological failure will be done by estimating percentages (categorical variables), average and median (continuous variables) with their intervals 95% confidence, overall and compared between the groups with virological success or failure per protocol (primary endpoint) or by intention to treat (secondary endpoint). The evolution of the parameters measured in children at birth, at 1, 3, and 6, months will be explored using non-parametric curves and compared between groups by repeated data taking into account the nonlinearity developments.
No interim analysis is planned.
No zidovudine will be administered at delivery in case of virological control, according to French Guidelines (Morlat Report 2015).
After delivery, the choice of maternal antiretrovial therapy (ART) is left to the discretion of the clinician and patient.
The mothers are followed up monthly until delivery and the last visit is planes at W4-W6 postpartum. Virological efficacy and safety will be assessed monthly.
In neonates, the prophylactic treatment, nevirapine oral solution, will be administrated as soon as possible in the first 12 hours of life and then for 14 days, once a day at a daily dose of 15 mg for a birthweight ≥ 2.5 kg ; 10 mg for a birthweight ≥ 2 kg and \< 2.5 kg and 2 mg / kg for a birthweight \< 2 kg (WHO Guidelines 2013 - French Guidelines, "Morlat Report" 2015).
Clinical and virological monitoring will be performed at Day 3, Day 15 in case of hospitalization, M1, M3 and M6.
Statistical Methods The analysis of the primary endpoint is the proportion of virological success (VL \< 50 copies/mL at delivery among women remaining on DRV/r). All changes in antiretroviral therapy because of VL ≥ 50 copies/ml will be considered as failures. Women who change antiretroviral therapy for other reasons and/or when pregnancy outcome is before 22 weeks of amenorrhea and \< 500g (non-viable pregnancy according to WHO) will be removed from the denominator.
Analysis of treatment changes, tolerance for the mother and child and factors associated with virological failure will be done by estimating percentages (categorical variables), average and median (continuous variables) with their intervals 95% confidence, overall and compared between the groups with virological success or failure per protocol (primary endpoint) or by intention to treat (secondary endpoint). The evolution of the parameters measured in children at birth, at 1, 3, and 6, months will be explored using non-parametric curves and compared between groups by repeated data taking into account the nonlinearity developments.
No interim analysis is planned.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: