Clinical Trials

MainTitle

A Prospective, Open-label Trial of Two ABC/3TC Based Regimens in Late Presenter naïve Patients (CD4 <200 Cells/µL)

This study is currently recruiting participants. (see Contacts and Locations)

Verified October 2016 by Cristina Mussini, University of Modena and Reggio Emilia

Sponsor
University of Modena and Reggio Emilia


Information provided by (Responsible Party)
Cristina Mussini, University of Modena and Reggio Emilia

ClinicalTrials.gov Identifier
NCT01900106

First received: July 5, 2013
Last updated: October 25, 2016
Last Verified: October 2016
History of Changes
Purpose

Purpose

1. PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to compare the 48-weeks virological response of two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

Secondary Objective: a) To compare immunological response at 48 weeks; b) To determine the safety and tolerability of the 2 regimens.

1.2 Study population: 350 in/out patients 1.3 Outcome Primary Endpoint

  • Proportion of patients with HIV RNA<50 copies/mL after 48 weeks Secondary Endpoints(s)
  • Change in CD4+ cell count from baseline through week 48
  • Time to virological rebound 1.4 Study design: Multicentre, parallel group, randomised,
open label, non-inferiority study 1.5 Treatment regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.

All drugs have been approved for the treatment of HIV infection. The study population will consist of 350 HIV-positive, HLA B5701-negative patients. At baseline, patients will be randomized 1:1 to start abacavir/lamivudine plus either raltegravir or darunavir/ritonavir. Randomization will be stratified on the basis of the screening CD4+ cell count (≤100 vs ≥100 cells/µL), to ensure balance across treatments groups 1.7 Criteria for Safety: Adverse events and laboratory assessments. 1.8 Statistical analysis: As this is a non-inferiority trial, we will calculate the difference in the proportions of patients experiencing the primary outcome in the two treatment arms and will calculate a 95% confidence interval for this. Non-inferiority of the raltegravir arm will be demonstrated if the lower limit of the 95% confidence interval is greater than -12%. In case non-inferiority will be met, analyses for superiority will be performed.

Condition Intervention Phase
HIV Infection

Drug : abacavir/lamivudine + raltegravir
Drug : abacavir/lamivudine + darunavir/ritonavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Open-label Trial of Two Abacavir/Lamivudine Based Regimen (ABC/3TC + Darunavir/Ritonavir or ABC/3TC + Raltegravir) in Late Presenter naïve Patients (With CD4 Count <200 Cells/µL - Advanced HIV Disease)

Further study details as provided by Cristina Mussini, University of Modena and Reggio Emilia:

Primary Outcome Measures

  • HIV RNA Viral Load [ Time Frame: baseline and week 48 ]
    The proportion of patients attaining an HIV RNA level <50 copies/mL after 48 weeks will be the primary outcome.

Estimated Enrollment: 350
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: abacavir/lamivudine + raltegravir
abacavir/lamivudine + raltegravir
Drug: abacavir/lamivudine + raltegravir

abacavir/lamivudine + raltegravir

Other Name:
  • Kivexa
  • Isentress

Active Comparator: ABC/3TC + DRV/r
abacavir/lamivudine + darunavir/ritonavir
Drug: abacavir/lamivudine + darunavir/ritonavir

abacavir/lamivudine + darunavir/ritonavir

Other Name:
  • Kivexa
  • Prezista
  • Norvir

Detailed Description:

  1. PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to compare the 48-weeks virological response of two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.
  2. 1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

Secondary Objective:
  1. To compare immunological response at 48 weeks;
  2. To determine the safety and tolerability of the 2 regimens. 1.2 Study population: 350 inpatients or outpatients will be randomized 1.3 Outcome Primary Endpoint
    • Proportion of patients with undetectable viremia (HIV RNA<50 copies/mL) after 48 weeks Secondary Endpoints(s)
    • Change in CD4+ cell count from baseline through week 48
    • Time to virological rebound Safety endpoints
    • Incidence of adverse events (AEs)
    • Incidence of serious adverse events (SAEs)
    • Discontinuations due to adverse events
    • Incidence of grade 3 or 4 laboratory abnormalities. 1.4 Study design Multicentre,
    parallel group, randomised, open label, non-inferiority study 1.5 Planned sample size: The planned sample size for this trial is 350 patients 1.6 Treatment regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.

All drugs have been approved for the treatment of HIV infection. Administration: oral The study population will consist of 350 HIV-positive, HLA B5701-negative patients. At baseline, patients will be randomized 1:1 to start abacavir/lamivudine plus either raltegravir or darunavir/ritonavir. Randomization will be stratified on the basis of the screening CD4+ cell count (≤100 vs ≥100 cells/µL), to ensure balance across treatments groups 1.7 Criteria for Safety: Adverse events and laboratory assessments. 1.8 Statistical analysis: As this is a non-inferiority trial, we will calculate the difference in the proportions of patients experiencing the primary outcome in the two treatment arms and will calculate a 95% confidence interval for this. Non-inferiority of the raltegravir arm will be demonstrated if the lower limit of the 95% confidence interval is greater than -12%. In case non-inferiority will be met, analyses for superiority will be performed.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 64 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. Males or females (inpatients or outpatients) aged 18-64 years who are HIV-1 antibody seropositive, with a CD4 count <200 cells/uL.
    2. All patients should be antiretroviral-naive
    3. All patients should be HLA B57 or HLA B5701 negative
    4. Patients must have an HIV RNA level <500,000 copies/mL
    5. Patients with an active opportunistic infection could be enrolled as long as this was diagnosed more than 2 weeks prior to screening.
    6. Patients must meet the following laboratory criteria. Neutrophil count > 1,000 cells/mm3 Haemoglobin > 9.0 grams/dl (men and women) Platelet count ≥ 75,000 cells/mm3 Alkaline phosphatase < 3.0 the upper limit of normal ALT and AST < 3.9 times the upper limit of normal Total bilirubin < 1.5 times the upper limit of normal.
    7. Female patients of childbearing potential must be willing to use a reliable form of contraception, which will include a medically approved form of barrier contraception.
    8. Patients must be able to provide written consent to comply with study requirements.


Exclusion Criteria:
    1. Patients with genotypic mutations for any of the study drugs.
    2. Patients with an opportunistic infection diagnosed in the 2 weeks prior to screening.
    3. Female patients who are pregnant or breastfeeding.
    4. Patients who are receiving any investigational drug or anti-neoplastic radiotherapy/chemotherapy other than local skin radiotherapy within 12 weeks before randomization.
    5. Patients with a current history of intravenous drug abuse, alcohol or substance abuse.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01900106

Contacts

Contact:   Cristina - Mussini, Professor +390594222466 cristina.mussini@unimore.it
Contact:   Cristina - Mussini, Professor +390594223673 cristina.mussini@unimore.it

Locations

Italy
University of Modena and Reggio Emilia Recruiting
Modena, Italy, 41124
Contact: Cristina - Mussini, Professor    +390594222466    cristina.mussini@unimore.it

Sponsors and Collaborators

University of Modena and Reggio Emilia

Investigators

Principal Investigator: Cristina - Mussini, Professor University of Modena and ReggioEmilia
More Information

More Information


Responsible Party: Cristina Mussini, Professor, University of Modena and Reggio Emilia  
ClinicalTrials.gov Identifier: NCT01900106   History of Changes  
Other Study ID Numbers: RTLP (PRADAR)  
  2011-005973-21  
Study First Received: July 5, 2013  
Last Updated: October 25, 2016  
Individual Participant Data    
Plan to Share IPD: No  

Keywords provided by Cristina Mussini, University of Modena and Reggio Emilia:

late presenter
naïve
advanced HIV disease

Additional relevant MeSH terms:
HIV Infections
Ritonavir
Darunavir
Lamivudine
Raltegravir Potassium
Abacavir
Dideoxynucleosides

ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.