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)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2013 by University of Modena and Reggio Emilia
Sponsor:
Information provided by (Responsible Party):
Cristina Mussini, University of Modena and Reggio Emilia
ClinicalTrials.gov Identifier:
NCT01900106
First received: July 5, 2013
Last updated: July 11, 2013
Last verified: July 2013
  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:

  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.


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: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


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

Primary Outcome Measures:
  • HIV RNA Viral Load [ Time Frame: baseline and week 48 ] [ Designated as safety issue: No ]
    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 Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: abacavir/lamivudine + raltegravir
abacavir/lamivudine + raltegravir
Drug: abacavir/lamivudine + raltegravir
Active Comparator: abacavir/lamivudine + darunavir/ritonavir
abacavir/lamivudine + darunavir/ritonavir
Drug: abacavir/lamivudine + darunavir/ritonavir

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
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
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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Cristina Mussini, Professor, University of Modena and Reggio Emilia
ClinicalTrials.gov Identifier: NCT01900106     History of Changes
Other Study ID Numbers: RTLP, 2011-005973-21
Study First Received: July 5, 2013
Last Updated: July 11, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Modena and Reggio Emilia:
late presenter
naïve
advanced HIV disease

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Darunavir
Lamivudine
Abacavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014