Clinical trial NCT00552240: Nevirapine vs. Atazanavir Boosted With Ritonavir on a Background of Truvada in Human Immunodeficiency Virus (HIV) Infected Naive Patients (NEwArT)
Official title: Comparison Atazanavir/Ritonavir (ATV/r) vs Nevirapine (NVP) Twice a Day (Bid) on Truvada Backbone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-11-01
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this clinical trial is to compare the efficacy and safety of ritonavir (RTV)-boosted atazanavir with nevirapine, each on a background of emtricitabine and tenofovir disoproxil fumarate (DF).


Eligibility criteria: Inclusion criteria:

1. Signed informed consent in accordance with Good Clinical Practice (GCP) and local regulatory requirements prior to trial participation
2. HIV-1- infected males or females greater than or equal to 18 years of age with documented positive serology Enzyme-linked Immuno Sorbert Assay (ELISA) confirmed by Western blot
3. No prior nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) use of more than 10 days AND
4. No prior use of other classes of antiretrovirals (ARVs) of more than 2 weeks duration
5. Males with CD4+ count less than 400 cells/mm cubed or females with CD4+ count less than 250 cells/mm cubed
6. NVP and ATV/r susceptibility on screening HIV-1 genotypic resistance assay
7. Adequate renal function defined as a calculated creatinine clearance greater than or equal to50 ml/min according to the Cockcroft-Gault formula
8. Karnofsky score greater than or equal to 70 (see Appendix 10.7)
9. Acceptable medical history, as assessed by the investigator

Exclusion criteria:

1. History of active drug or alcohol abuse within 2 years prior to study entry (at the investigators discretion)
2. Hepatic cirrhosis with stage Child-Pugh B or C hepatic impairment
3. Female patients of child-bearing potential who:

   have a positive serum pregnancy test at screening, are breast feeding, are planning to become pregnant, are not willing to use a barrier method of contraception, or are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives
4. Laboratory parameters greater than Division of Aids (National Institute of Health, USA) (DAIDS) grade 2 (triglycerides greater than DAIDS grade 3, total cholesterol no restrictions, see Appendix 10.1)
5. Active hepatitis B or C disease, defined as HBsAg-positive or Hepatitis C Virus (HCV) RNA positive with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ALT/AST greater than2.5x Upper Limit of Normal (ULN) (greater than DAIDS grade 1)
6. Known hypersensitivity to any ingredients in nevirapine or atazanavir
7. Patients who are receiving concomitant treatments which are not permitted, as listed in Appendix 10.6
8. Use of other investigational medications within 30 days before study entry or during the trial
9. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2, chronic treatment with prednisone)
10. Patients with Progressive Multifocal Leukoencephalopathy (PML), visceral Kaposi's Sarcoma (KS), and/or any lymphoma
11. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at the screening visit
12. Patients who are receiving systemic chemotherapy

Primary outcomes:
measure: Number of Participants With Virologic Response (VR)
timeFrame: baseline to week 48
Secondary outcomes:
measure: Number of Participants With Virologic Response According to the Time to Loss of Virologic Response (TLOVR) Algorithm
timeFrame: baseline to week 48
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 48
timeFrame: baseline to week 48
measure: Number of Participants With Virologic Success (FDA Definition)
timeFrame: baseline to week 48
measure: Time to Virologic Response (First Confirmed Viral Load < 50 Copies/ml), All Participants
timeFrame: baseline to week 48
measure: Time to Virologic Response (First Confirmed Viral Load < 50 Copies/ml), Only Participants With Confirmed Viral Load < 50 Copies/ml
timeFrame: baseline to week 48
measure: Number of Participants With Loss of Virologic Response Following Confirmed Virologic Response
timeFrame: baseline to week 24 and week 48
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 2 of Treatment
timeFrame: baseline to week 2
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 4 of Treatment
timeFrame: baseline to week 4
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 6 of Treatment
timeFrame: baseline to week 6
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 8 of Treatment
timeFrame: baseline to week 8
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 12 of Treatment
timeFrame: baseline to week 12
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 24 of Treatment
timeFrame: baseline to week 24
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 36 of Treatment
timeFrame: baseline to week 36
measure: Number of Participants With HIV Viral Load < 50 Copies/ml at Week 48 of Treatment
timeFrame: baseline to week 48
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 2 of Treatment
timeFrame: baseline to week 2
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 4 of Treatment
timeFrame: baseline to week 4
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 6 of Treatment
timeFrame: baseline to week 6
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 8 of Treatment
timeFrame: baseline to week 8
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 12 of Treatment
timeFrame: baseline to week 12
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 24 of Treatment
timeFrame: baseline to week 24
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 36 of Treatment
timeFrame: baseline to week 36
measure: Number of Participants With HIV Viral Load < 400 Copies/ml at Week 48 of Treatment
timeFrame: baseline to week 48
measure: Number of Patients With Virologic Rebound to >400 Copies/ml
timeFrame: baseline to week 48
measure: AIDS Progression and Death: Number of Patients With a Treatment-emergent AIDS Defining Illness or an AIDS-defining Illness Leading to Death
timeFrame: baseline to week 48
measure: Change in CD4+ Cell Count From Baseline to Week 2.
timeFrame: baseline to week 2
measure: Change in CD4+ Cell Count From Baseline to Week 4.
timeFrame: baseline to week 4
measure: Change in CD4+ Cell Count From Baseline to Week 6.
timeFrame: baseline to week 6
measure: Change in CD4+ Cell Count From Baseline to Week 8.
timeFrame: baseline to week 8
measure: Change in CD4+ Cell Count From Baseline to Week 12.
timeFrame: baseline to week 12
measure: Change in CD4+ Cell Count From Baseline to Week 24.
timeFrame: baseline to week 24
measure: Change in CD4+ Cell Count From Baseline to Week 36.
timeFrame: baseline to week 36
measure: Change in CD4+ Cell Count From Baseline to Week 48.
timeFrame: baseline to week 48
measure: Change in Fasting Plasma Total Cholesterol Level
timeFrame: baseline to week 48
measure: Change in Fasting Plasma Triglycerides Level
timeFrame: baseline to week 48
measure: Change in Fasting High Density Lipoprotein (HDL) Cholesterol Level
timeFrame: baseline to week 48
measure: Change in Fasting Low Density Lipoprotein (LDL)Cholesterol Level
timeFrame: baseline to week 48
measure: Change in Fasting Total Cholesterol to High Density Lipoprotein (HDL) Ratio
timeFrame: baseline to week 48
measure: Change in Framingham Score
timeFrame: baseline to week 48
measure: Change in Revised Framingham Score According to the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group
timeFrame: baseline to week 48
measure: Change in Glomerular Filtration Rate (GFR) From Baseline to Week 48
timeFrame: baseline to week 48
measure: Percentage Adherence by Pill Count
timeFrame: baseline to week 48
measure: Number of Participants With Genotypic Resistance at the Time of Virologic Failure.
timeFrame: baseline to week 48
measure: Incidence of Patients With AIDS Progression at Each Visit
timeFrame: baseline to week 52
measure: Proportion of Patients Reporting CNS Side Effects of Any Severity
timeFrame: baseline to week 52
measure: Proportion of Patients Reporting Hepatic Events of Any Severity
timeFrame: baseline to week 52
measure: Proportion of Patients Reporting Rash of Any Severity
timeFrame: baseline to week 52
measure: Proportion of Patients With DAIDS Grade >= 2 Laboratory Abnormalities
timeFrame: baseline to week 52
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: 1100.1512.28 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1100.1512.20 Boehringer Ingelheim Investigational Site
state: California
city: Denver
country: United States
facility: 1100.1512.15 Boehringer Ingelheim Investigational Site
state: Colorado
city: Washington
country: United States
facility: 1100.1512.26 Boehringer Ingelheim Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: 1100.1512.17 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1100.1512.14 Boehringer Ingelheim Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: 1100.1512.23 Boehringer Ingelheim Investigational Site
state: Florida
city: Maywood
country: United States
facility: 1100.1512.29 Boehringer Ingelheim Investigational Site
state: Illinois
city: Neptune
country: United States
facility: 1100.1512.11 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Newark
country: United States
facility: 1100.1512.25 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Somers Point
country: United States
facility: 1100.1512.18 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Winston-Salem
country: United States
facility: 1100.1512.22 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: 1100.1512.21 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1100.1512.13 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 1100.1512.30 Boehringer Ingelheim Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: 1100.1512.19 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1100.1512.16 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1100.1512.24 Boehringer Ingelheim Investigational Site
state: Texas
city: Annandale
country: United States
facility: 1100.1512.27 Boehringer Ingelheim Investigational Site
state: Virginia
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: