Back to resultsDolutegravir + Rilpivirine Switch Study (DORISS) (DORISS)
Primary Purpose
HIV Infection, HAART-treated, Virologically Controlled
Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Arm 1 (intervention)
Arm 2 (control)
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infection focused on measuring Dolutegravir, Rilpivirine, PI- and NRTI- sparing ART regimen, switch study
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- HIV-1 infection
- Treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, or 1 NNRTI, or INI), unchanged for > 6 months, Intra-class substitution within past 6 months is not considered as a treatment change.
- Plasma HIV-RNA ≤ 50 copies/mL for > 2 years
- CD4 cell count > 350/mm3 for > 6 months
- No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen
- No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D.
- No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S
- Negative HBs Ag
- Informed consent form signed by patient and investigator
- A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study
- Patient covered with health insurance
- Effective contraception
Exclusion Criteria:
- HIV-2 infection
- Dialysis or severe renal failure (creatinine clearance < 30 ml/min)
- History of decompensated liver disease
- History of HIV-associated neurocognitive disorders
- AST or ALT > 5 x ULN
- Positive HBc Ac and negative HBs Ac
- Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug
- Current pregnancy or breastfeeding
- Patient involved in another research that precludes enrolment in another trial
- Patient under guardianship, or deprived of liberty by a court or administrative decision.
Sites / Locations
- CHU Guadeloupe
- CHU de Fort de France
- Chu Jean Minjoz
- Hôpital Avicenne
- Hôpital Jean Verdier
- CHU de Bordeaux
- CHU de DIJON
- CHD La Roche sur Yon
- CHU Kremlin Bicêtre
- Hôpital Perpetuel Secours
- CHU de Nantes
- Hôpital Saint Louis
- CHU BICHAT - Claude Bernard
- CHU Hôtel Dieu Paris
- Hôpital La Pitié Salpêtrière
- Hôpital Necker - enfants Malades
- Hôpital Européen Georges Pompidou
- CHU de Rennes - Hôpital Pontchaillou
- CH Delafontaine
- CHU Saint Etienne
- CHU de Strasbourg
- Hôpital FOCH
- CHU Toulouse
- CHRU de Tours
- CHU de Nancy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm 1 (intervention)
Arm 2 (control)
Arm Description
Dolutegravir 50 mg/d + Rilpivirine 25 mg/d qd orally (intake during a meal)
Continuation of existing HAART at the time of randomization
Outcomes
Primary Outcome Measures
Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)
Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks
Secondary Outcome Measures
Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48
Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48
Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL
Measure of the profile of genotypic resistance in plasma in case of virologic failure
Percentage of patients who discontinued or changed the strategy of the study
Measure of the HIV-DNA between day 0 and week 48
Evolution of the HIV-DNA between Day 0 and week 48
Measure of CD4 lymphocytes at week 24 compared to day 0
Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0
Measure of CD4 lymphocytes at Week 48 compared to Day 0
Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0
Number of patients with adverse events of grade 2 to 4
Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events
Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0
Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0
Measure of changes in serum lipid parameters at week 48 to Day 0
Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0
Measure of changes in fat mass distribution at week 24 compared to Day 0
Changes in fat mass distribution at Week 24 compared to Day 0
Measure of changes in fat mass distribution at Week 48 compared to Day 0
Changes in fat mass distribution at Week 48 compared to Day 0
Measure of adherence to treatment at Week 24 compared to Day 0
Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire
Measure of adherence to treatment at Week 48 compared to Day 0
Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire
Measure of patient satisfaction for their treatment at Day 0
Assessment of patient satisfaction for their treatment at D0 by questionnaire
Measure of patient satisfaction for their treatment at Week 24
Assessment of patient satisfaction for their treatment at Week 24 by questionnaire
Measure of patient satisfaction for their treatment at Week 48
Assessment of patient satisfaction for their treatment at Week 48 by questionnaire
Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
Measure of the profile of genotypic resistance in plasma in case of virologic failure
Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL
Full Information
NCT ID
NCT02069834
First Posted
February 18, 2014
Last Updated
August 27, 2015
Sponsor
Nantes University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02069834
Brief Title
Dolutegravir + Rilpivirine Switch Study (DORISS)
Acronym
DORISS
Official Title
Dolutegravir + Rilpivirine Switch Study (DORISS): Pilot and Noninferiority Trial Comparing Dolutegravir + Rilpivirine vs. Continued HAART (Highly Active Antiretroviral Therapy) in Patients With Plasma HIV RNA ≤ 50 Copies/mL for at Least 2 Years
Study Type
Interventional
2. Study Status
Record Verification Date
August 2015
Overall Recruitment Status
Withdrawn
Why Stopped
One of the both Funder partners decided to stop the study before the initiation : thus no product provided and no funding to realize the study
Study Start Date
May 2014 (undefined)
Primary Completion Date
October 2017 (Anticipated)
Study Completion Date
October 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent).
The main secondary objectives are the following:
% of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48
% of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48
% of virological failure defined by two consecutive plasma viral load > 50 copies/mL
Profile of genotypic resistance in case of virological failure.
The trial will be conducted according to the design below, in 3 steps:
Step 1: enrollment of 80 patients (40 in each arm)
Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed.
Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly > 70%, which translates in a maximum of 6 virologic failures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection, HAART-treated, Virologically Controlled
Keywords
Dolutegravir, Rilpivirine, PI- and NRTI- sparing ART regimen, switch study
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 (intervention)
Arm Type
Experimental
Arm Description
Dolutegravir 50 mg/d + Rilpivirine 25 mg/d qd orally (intake during a meal)
Arm Title
Arm 2 (control)
Arm Type
Active Comparator
Arm Description
Continuation of existing HAART at the time of randomization
Intervention Type
Drug
Intervention Name(s)
Arm 1 (intervention)
Intervention Description
Dolutegravir 50 mg/j + Rilpivirine 25 mg/j qd orally (intake during meal)
Intervention Type
Drug
Intervention Name(s)
Arm 2 (control)
Intervention Description
Continuation of existing HAART at the time of randomization
Primary Outcome Measure Information:
Title
Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)
Time Frame
Week 16
Title
Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48
Time Frame
Week 48
Title
Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48
Time Frame
Week 48
Title
Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL
Time Frame
Week 48
Title
Measure of the profile of genotypic resistance in plasma in case of virologic failure
Time Frame
Week 48
Title
Percentage of patients who discontinued or changed the strategy of the study
Time Frame
Week 48
Title
Measure of the HIV-DNA between day 0 and week 48
Description
Evolution of the HIV-DNA between Day 0 and week 48
Time Frame
W48
Title
Measure of CD4 lymphocytes at week 24 compared to day 0
Description
Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0
Time Frame
Week 24
Title
Measure of CD4 lymphocytes at Week 48 compared to Day 0
Description
Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0
Time Frame
Week 48
Title
Number of patients with adverse events of grade 2 to 4
Description
Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events
Time Frame
Week 48
Title
Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0
Description
Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0
Time Frame
Week 24
Title
Measure of changes in serum lipid parameters at week 48 to Day 0
Description
Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0
Time Frame
Week 48
Title
Measure of changes in fat mass distribution at week 24 compared to Day 0
Description
Changes in fat mass distribution at Week 24 compared to Day 0
Time Frame
Week 24
Title
Measure of changes in fat mass distribution at Week 48 compared to Day 0
Description
Changes in fat mass distribution at Week 48 compared to Day 0
Time Frame
Week 48
Title
Measure of adherence to treatment at Week 24 compared to Day 0
Description
Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire
Time Frame
Week 24
Title
Measure of adherence to treatment at Week 48 compared to Day 0
Description
Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire
Time Frame
Week 48
Title
Measure of patient satisfaction for their treatment at Day 0
Description
Assessment of patient satisfaction for their treatment at D0 by questionnaire
Time Frame
Day 0
Title
Measure of patient satisfaction for their treatment at Week 24
Description
Assessment of patient satisfaction for their treatment at Week 24 by questionnaire
Time Frame
Week 24
Title
Measure of patient satisfaction for their treatment at Week 48
Description
Assessment of patient satisfaction for their treatment at Week 48 by questionnaire
Time Frame
Week 48
Title
Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
Description
Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
Time Frame
Week 24
Title
Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
Description
Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
Time Frame
Week 48
Title
Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
Description
Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
Time Frame
Week 4
Title
Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
Description
Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
Time Frame
Week 24
Title
Measure of the profile of genotypic resistance in plasma in case of virologic failure
Time Frame
Week 24
Title
Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
HIV-1 infection
Treatment with suppressive triple HAART (2 NRTI + either 1 PI/r, or 1 NNRTI, or INI), unchanged for > 6 months, Intra-class substitution within past 6 months is not considered as a treatment change.
Plasma HIV-RNA ≤ 50 copies/mL for > 2 years
CD4 cell count > 350/mm3 for > 6 months
No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen
No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D.
No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S
Negative HBs Ag
Informed consent form signed by patient and investigator
A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study
Patient covered with health insurance
Effective contraception
Exclusion Criteria:
HIV-2 infection
Dialysis or severe renal failure (creatinine clearance < 30 ml/min)
History of decompensated liver disease
History of HIV-associated neurocognitive disorders
AST or ALT > 5 x ULN
Positive HBc Ac and negative HBs Ac
Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug
Current pregnancy or breastfeeding
Patient involved in another research that precludes enrolment in another trial
Patient under guardianship, or deprived of liberty by a court or administrative decision.
Facility Information:
Facility Name
CHU Guadeloupe
City
Point-a-pitre
State/Province
Guadeloupe
ZIP/Postal Code
97159
Country
France
Facility Name
CHU de Fort de France
City
Fort de France
State/Province
Martinique
ZIP/Postal Code
87261
Country
France
Facility Name
Chu Jean Minjoz
City
Besançon
ZIP/Postal Code
25030
Country
France
Facility Name
Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93000
Country
France
Facility Name
Hôpital Jean Verdier
City
Bondy
ZIP/Postal Code
93140
Country
France
Facility Name
CHU de Bordeaux
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU de DIJON
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
CHD La Roche sur Yon
City
La Roche sur Yon
ZIP/Postal Code
85925
Country
France
Facility Name
CHU Kremlin Bicêtre
City
Le Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Hôpital Perpetuel Secours
City
Levallois-perret
ZIP/Postal Code
92300
Country
France
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital Saint Louis
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
CHU BICHAT - Claude Bernard
City
Paris cedex 18
ZIP/Postal Code
75877
Country
France
Facility Name
CHU Hôtel Dieu Paris
City
Paris
ZIP/Postal Code
75004
Country
France
Facility Name
Hôpital La Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hôpital Necker - enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
ZIP/Postal Code
75908
Country
France
Facility Name
CHU de Rennes - Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
CH Delafontaine
City
Saint Denis
ZIP/Postal Code
93200
Country
France
Facility Name
CHU Saint Etienne
City
Saint Etienne
ZIP/Postal Code
42055
Country
France
Facility Name
CHU de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Hôpital FOCH
City
Suresnes
ZIP/Postal Code
92150
Country
France
Facility Name
CHU Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
CHRU de Tours
City
Tours Cedex 09
ZIP/Postal Code
37044
Country
France
Facility Name
CHU de Nancy
City
VANDOEUVRE LES NANCY cedex
ZIP/Postal Code
54511
Country
France
12. IPD Sharing Statement
Learn more about this trial
Dolutegravir + Rilpivirine Switch Study (DORISS)
We'll reach out to this number within 24 hrs