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Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy (TRULIGHT)

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ClinicalTrials.gov Identifier: NCT02302547
Recruitment Status : Completed
First Posted : November 27, 2014
Last Update Posted : December 4, 2018
Sponsor:
Collaborators:
HOSPITAL, ORLEANS
Poitiers University Hospital
Centre Hospitalier de La Rochelle
HOSPITAL, SAINTES
HOSPITAL, FOCH
HOSPITAL, CAEN
HOSPITAL, HENRI MONDOR
HOSPITAL, HOTEL DIEU
HOSPITAL, CHARTRES
HOSPITAL, SAINT LOUIS
Tourcoing Hospital
Central Hospital, NIORT
Tenon Hospital, Paris
Central Hospital, Nancy, France
University Hospital, Rouen
Information provided by (Responsible Party):
University Hospital, Tours

Tracking Information
First Submitted Date  ICMJE October 14, 2014
First Posted Date  ICMJE November 27, 2014
Last Update Posted Date December 4, 2018
Actual Study Start Date  ICMJE December 2014
Actual Primary Completion Date August 23, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2014)
Viral Load at 48 weeks [ Time Frame: 48 weeks ]
Percentage of patient having a viral load < 50 copies/ml in each arm reductive anti retroviral strategy from an original backbone of 2 Nucleoside reverse transcriptase inhibitors (Tenofovir Disoproxil Fumarate+ Emtricitabine) coupled to a third agent, towards a therapeutic strategy containing the backbone therapy alone (Truvada®).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Change from week 4 in Viral load at 48 weeks [ Time Frame: between 4 weeks and 48 weeks ]
    percentage of patients having a viral load between 50 and 400 copies/ml between week 4 and week 48
  • CD 4 level in each arm [ Time Frame: 48 weeks ]
    delta CD 4 measurement in each arm
  • Change from day 0 in HIV - DNA at week 48 [ Time Frame: day 0 and 48 weeks ]
    HIV DNA evolution between day 0 and week 48 in each arm
  • RNA and DNA viral load (sub study) [ Time Frame: Time Frame: Week 24 to Week 48 ]
    RNA and DNA viral load in the genital tract (cervico-vaginal secretions or sperm): comparison between arms
Original Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2014)
  • Change from week 4 in Viral load at 48 weeks [ Time Frame: between 4 weeks and 48 weeks ]
    percentage of patients having a viral load between 50 and 400 copies/ml between week 4 and week 48
  • CD 4 level in each arm [ Time Frame: 48 weeks ]
    delta CD 4 measurement in each arm
  • Change from day 0 in HIV - DNA at week 48 [ Time Frame: day 0 and 48 weeks ]
    HIV DNA evolution between day 0 and week 48 in each arm
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy
Official Title  ICMJE Randomized Clinical Trial to Evaluate the Interest of a Down-scaled Treatment Strategy Using Dual Therapy (Nucleoside Analogs) in HIV Infected Patients Already Being Treated Using Triple Therapy, Who Present With a Successful Virological Control and for Which the HIV Reservoir is Low to Moderate
Brief Summary

In the early 2000s, the "TRILEGE©" study was realized to determine if the reductive anti retroviral strategy from an initial triple therapy (based on a protease inhibitor as the third agent) towards a dual therapy of nucleoside analogs (in particular the association of "zidovudine +lamivudine") for patients infected by HIV and stabilized for at least 3 months at a threshold value of 400 copies/ml, would allow to obtain a well-controlled plasmatic viral load, with an aim to reduce the long-term side effects of the treatment.

The afore mentioned study showed that the reductive anti retroviral strategy was a failure. No study has as yet to revaluate this strategy, in particular in the current context of antiretroviral treatments.

Indeed, modern nucleoside inhibitors (Kivexa®, Truvada®) have extended half-lives as well as a superior intrinsic power as compared to treatments proposed in the initial "TRILEGE©" study. Furthermore, the better quality of current triple therapy (as compared to that used 10 years ago) has lead to substantial viral reservoir reduction.

Currently, a small number of patients is being successfully treated in the long-term (viral load < 20 copies/ml) using nucleoside analog dual therapy. The particular characteristics of these patients have yet to be thoroughly investigated.

The patients concerned were all treated prematurely before ever passing below 200 lymphocytes T CD4/mm3. It occurred that all these patients presented a low viral reservoir as measured by HIV DNA quantification (< 2,7 log copies/106 PBMC).

Therefore, by targeting patients who have (1) a strong immune restoration, (2) a low HIV DNA value and (3) a very good observance, the investigators emit the hypothesis that, reductive anti retroviral strategy that would consist in changing from a conventional triple therapy towards a Nucleoside reverse-transcriptase inhibitors dual therapy, could allow for durable control of viral replication with the concomitant benefice of reduced antiretroviral side effects and cost.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • Drug: triple therapy
    Dosage treatment and usual prescription
    Other Names:
    • Tenofovir+Emtricitabine+Third agent (Including a non nucleoside reverse transcriptase inhibitor: efavirenz or nevirapine or etravirine or rilpivirine
    • Tenofovir+Emtricitabine+Third agent (Including a ritonavir-boosted protease inhibitor : saquinavir or indinavir or fosamprenavir or tipranavir or darunavir or atazanavir or lopinavir
    • Tenofovir+Emtricitabine+Third agent (Including an unboosted protease inhibitor: atazanavir or indinavir
    • Tenofovir+Emtricitabine+Third agent (Including an integrase inhibitor raltegravir or dolutegravir or cobicistat-boosted elvitegravir
    • Tenofovir+Emtricitabine+Third agent (Including a fusion inhibitor: enfuvirtide or a CCR5 antagonist :maraviroc
  • Drug: dual therapy
    1 tablet (200mg/245mg) daily for 48 weeks
    Other Name: Truvada®
Study Arms  ICMJE
  • Active Comparator: triple therapy
    Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor) + third agent (boosted protease inhibitor or unboosted protease inhibitor or integrase inhibitor or celsentri or non-nucleoside reverse transcriptase inhibitor).
    Intervention: Drug: triple therapy
  • Experimental: dual therapy
    Truvada®"245mg":oral administration Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)
    Intervention: Drug: dual therapy
Publications * Hocqueloux L, Gubavu C, Prazuck T, De Dieuleveult B, Guinard J, Sève A, Mille C, Gardiennet E, Lopez P, Rouzioux C, Lefeuvre S, Avettand-Fènoël V. Genital Human Immunodeficiency Virus-1 RNA and DNA Shedding in Virologically Suppressed Individuals Switching From Triple- to Dual- or Monotherapy: Pooled Results From 2 Randomized, Controlled Trials. Clin Infect Dis. 2020 Apr 15;70(9):1973-1979. doi: 10.1093/cid/ciz511.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 5, 2017)
224
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2014)
250
Actual Study Completion Date  ICMJE September 21, 2018
Actual Primary Completion Date August 23, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HIV-1 infected patient
  • Initial TT ARV started above (or equal to) 150 / mm3 LT CD4, and 18 months prior to inclusion in the study
  • Ongoing antiretroviral therapy combining tenofovir + emtricitabine + a 3rd agent (IP / r, IP, NNRTI, II, Inhibitors) with at least one undetectable viral load (CV <50 copies / mL) after introduction of the latter treatment.
  • Patient in virological success: CV <50 copies / mL for at least 12 months, including visit to selection.
  • Absence of previous therapeutic failure: no viral load ≥ 200 copies / mL (after 6 months of treatment) (Except in the case of a justified therapeutic interruption: travel, stock-out ...) and of obtaining success Virologic after introduction of treatment, without concept of genotypic resistance known to the ARVs used.
  • Cellular DNA-HIV <2.7 log copies / 106 PBMC
  • Zenith RNA-HIV <150,000 copies / ml (excluding viral load values during primary infection if it is documented)
  • No genotypic resistance to currently used and known ARVs
  • Patient who has given written informed consent
  • Affiliate or beneficiary of a social security scheme
  • Patient followed on an outpatient basis, age ≥ 18 years.

Exclusion Criteria:

  • Non-compliant patient
  • Subject is pregnant, or lactating, or of childbearing potential and without contraception
  • Active opportunistic infections
  • Major overweight (BMI ≥ 40)
  • Severe renal pathology (creatinine clearance < 30ml/min)
  • Cirrhosis or severe liver failure (factor V < 50%)
  • Prognosis threatened within 6 months
  • Circumstances that may impair judgment or understanding of the information given to the patient
  • Malabsorption syndromes
  • The following laboratory criteria:

    • Serum ASAT,ALAT > 5 x upper limit of normal (ULN)
    • Thrombocytopenia with platelet count < 50.000/ml
    • Anemia with hemoglobin < 8g/dl
    • Polynuclear neutrophil count < 500/mm3
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02302547
Other Study ID Numbers  ICMJE PHAO13-TP/TRULIGHT
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Tours
Study Sponsor  ICMJE University Hospital, Tours
Collaborators  ICMJE
  • HOSPITAL, ORLEANS
  • Poitiers University Hospital
  • Centre Hospitalier de La Rochelle
  • HOSPITAL, SAINTES
  • HOSPITAL, FOCH
  • HOSPITAL, CAEN
  • HOSPITAL, HENRI MONDOR
  • HOSPITAL, HOTEL DIEU
  • HOSPITAL, CHARTRES
  • HOSPITAL, SAINT LOUIS
  • Tourcoing Hospital
  • Central Hospital, NIORT
  • Tenon Hospital, Paris
  • Central Hospital, Nancy, France
  • University Hospital, Rouen
Investigators  ICMJE
Principal Investigator: LOUIS BERNARD, Pr CHRU de TOURS
Principal Investigator: GWENAEL LE MOAL, Dr Poitiers University Hospital
Principal Investigator: MARIAM RONCATO- SABERAN, Dr CH de LA ROCHELLE
Principal Investigator: THIERRY PASDELOUPS, Dr CH de SAINTES
Principal Investigator: DAVID ZUCMAN, Dr HOPITAL de FOCH
Principal Investigator: RENAUD VERDON, Pr University Hospital, Caen
Principal Investigator: SEBASTIEN GALLIEN, Pr CHU d'HENRI MONDOR
Principal Investigator: JEAN - PAUL VIARD, Pr CH d'HOTEL DIEU
Principal Investigator: MARC LESTELLE, Dr CH de CHARTRES
Principal Investigator: JEAN - MICHEL MOLINA, Pr CHU SAINT LOUIS
Principal Investigator: FAÏZA AJANA, Dr CH de TOURCOING
Principal Investigator: SIMON SUNDER, Dr CH de NIORT
Principal Investigator: Gilles PIALOUX, Pr HOSPITAL TENON
Principal Investigator: Thierry MAY, Dr CHU de Nancy
Principal Investigator: Manuel ETIENNE, Dr CHU de ROUEN
PRS Account University Hospital, Tours
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP