Tipranavir/Ritonavir vs. Genotypically Defined Protease Inhibitor/Ritonavir in HIV Patients (RESIST-2)

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00144170
First received: September 2, 2005
Last updated: June 23, 2014
Last verified: April 2014

September 2, 2005
June 23, 2014
February 2003
October 2008   (final data collection date for primary outcome measure)
  • Treatment Response at Week 48 [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Time to Treatment Failure Through 48 Weeks of Treatment [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as 0 for patients who never achieve TR otherwise time to treatment failure is the earliest time of death, discontinuation of the study drug or introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background, or the first of two consecutive visits with Log(baseline Viral Load) - Log(on-treatment Viral Load) < 1.
The primary endpoints of the study are the proportion of patients with a treatment response at 48 weeks and the time to treatment failure through 48 weeks.
Complete list of historical versions of study NCT00144170 on ClinicalTrials.gov Archive Site
  • Treatment Response at Week 2 [ Time Frame: week 2 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 4 [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 8 [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 16 [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 32 [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 40 [ Time Frame: week 40 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 56 [ Time Frame: week 56 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 64 [ Time Frame: week 64 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 72 [ Time Frame: week 72 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 80 [ Time Frame: week 80 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 88 [ Time Frame: week 88 ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Treatment Response at Week 96 [ Time Frame: after 96 weeks of treatment ] [ Designated as safety issue: No ]
    Patients who experienced treatment response. Treatment response (TR) is defined as two consecutive VL ≥ 1 log10 below baseline without discontinuation of study drug, change in anti-retroviral background, or rebound
  • Time to Treatment Failure Through 96 Weeks of Treatment [ Time Frame: after 96 weeks of treatment ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as 0 for patients who never achieve TR otherwise time to treatment failure is the earliest time of death, discontinuation of the study drug or introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background, or the first of two consecutive visits with Log(baseline Viral Load) - Log(on-treatment Viral Load) < 1.
  • Time to Confirmed Virologic Failure Through 48 Weeks of Treatment [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]
    Time to virologic failure is defined as the time from the start of treatment to the last measurement where the Log(baseline viral load)-Log(on-treatment viral load)>1 before a 2 consecutive measurements where Log(baseline viral load)-Log(on-treatment viral load)<1.
  • Time to Confirmed Virologic Failure Through 96 Weeks of Treatment [ Time Frame: after 96 weeks of treatment ] [ Designated as safety issue: No ]
    Time to virologic failure is defined as the time from the start of treatment to the last measurement where the Log(baseline viral load)-Log(on-treatment viral load)>1 before a 2 consecutive measurements where Log(baseline viral load)-Log(on-treatment viral load)<1.
  • Virologic Response [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 4 [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 8 [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 16 [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 32 [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 40 [ Time Frame: week 40 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 48 [ Time Frame: week 48 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 56 [ Time Frame: week 56 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 64 [ Time Frame: week 64 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 80 [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 88 [ Time Frame: Week 88 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Virologic Response at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1
  • Median Change From Baseline in Viral Load (Week 2) [ Time Frame: Baseline to Week 2 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 4) [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 8) [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 16) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 24) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 32) [ Time Frame: Baseline to Week 32 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 40) [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 48) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 56) [ Time Frame: Baseline to Week 56 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 64) [ Time Frame: Baseline to Week 64 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 72) [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 80) [ Time Frame: Baseline to Week 80 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 88) [ Time Frame: Baseline to Week 88 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load (Week 96) [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Virologic Response at Week 40 [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Viral Load Nadir During Study Treatment Through 96 Weeks [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 64 [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 80 [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 88 [ Time Frame: week 88 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response at Week 96 [ Time Frame: week 96 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<400 copies/mL
  • Virologic Response [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Viral Load < 50 copies/mL
  • Virologic Response at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 40 [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 64 [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 80 [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 88 [ Time Frame: Week 88 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Virologic Response at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Virologic response defined as Viral Load<50 copies/mL
  • Mean Change From Baseline in CD4+ Cell Count (Week 2) [ Time Frame: Baseline to Week 2 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 4) [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 8) [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 16) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 24) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 32) [ Time Frame: Baseline to Week 32 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 40) [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 48) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 56) [ Time Frame: Baseline to Week 56 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 64) [ Time Frame: Baseline to Week 64 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 72) [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 80) [ Time Frame: Baseline to Week 80 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 88) [ Time Frame: Baseline to Week 88 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in CD4+ Cell Count (Week 96) [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Time to New Centers for Disease Control (CDC) Class C Progression Event or Death. [ Time Frame: up to 75 weeks of treatment ] [ Designated as safety issue: No ]

    Time to death or occurrence of AIDS-defining condition according to the US Centers for Disease Control and Prevention case definition.

    The median and quartiles are underestimated since more than 92% of the observations (in both treatment arms) were censored and the estimation was restricted to the largest observed event time.

The key secondary endpoint of the study to be assessed at an interim analysis, is the proportion of patients with a virologic response at 16 weeks. Additional secondary endpoints are listed in the protocol.
Not Provided
Not Provided
 
Tipranavir/Ritonavir vs. Genotypically Defined Protease Inhibitor/Ritonavir in HIV Patients (RESIST-2)
Randomized, Open-label, Comparative Safety and Efficacy Study of Tipranavir Boosted With Low Dose Ritonavir (TPV/RTV) Versus Genotypically-defined Protease Inhibitor/Ritonavir (PI/RTV) in Multiple Antiretroviral Drug-experienced Patients (RESIST 2: Randomized Evaluation of Strategic Intervention in Multi-Drug Resistant Patients With Tipranavir)

The objective of this study is to demonstrate the safety and efficacy of tipranavir/ritonavir versus an active control arm in highly treatment experienced Human immunodeficiency virus-1 infected patients. Patients must have a viral load > =1000 cells/mL, and genotype indicating at least one resistance conferring protease inhibitor-mutation as determined from a predefined panel of mutations. Any CD4+ count is acceptable.

Not Provided
Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
HIV Infections
  • Drug: Tipranavir (with low dose ritonavir)
  • Drug: Comparator protease inhibitor(CPI)/low dose ritonavir(r)
  • Tipranavir(TPV)/low dose ritonavir(r)
    Intervention: Drug: Tipranavir (with low dose ritonavir)
  • Comparator protease inhibitor(CPI)/low dose ritonavir(r)
    Intervention: Drug: Comparator protease inhibitor(CPI)/low dose ritonavir(r)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
882
Not Provided
October 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Signed informed consent prior to trial participation.
  2. Human immunodeficiency virus-1 infected males or females >=18 years of age.
  3. Screening genotypic resistance report indicating both of the following:

    • at least one primary protease mutation at the following sites 30N, 46I/L, 48V, 50V, 82A/F/L/T, 84V or 90M , and
    • no more than two protease mutations on codons 33, 82, 84, or 90.
  4. At least 3 consecutive months experience taking antiretrovirals from each of the classes of Nucleoside reverse transcriptase inhibitor(s), Non-nucleoside reverse transcriptase inhibitor(s), and Protease inhibitor(s) at some point in treatment history,

    • with at least 2 Protease inhibitor-based regimens (minimum 3 months of exposure of each), one of which must be part of the current regimen, and
    • current Protease inhibitor-based antiretroviral medication regimen for at least 3 months prior to randomisation.
  5. Human immunodeficiency virus-1 viral load >=1000 copies/mL at screening.
  6. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if the following apply:

    • Total cholesterol <=400 mg/dl or 10,36 mm/L.
    • Total triglycerides <=750 mg/dl or 8,5 mm/L.
    • Alanine aminotransferase <=3x upper limit of normal and aspartate aminotransferase <=2.5x upper limit of normal.
    • Any Grade gamma-glutamyl transpeptidase is acceptable.
    • Any Grade creatinine kinase is acceptable as long as there is no concurrent myopathy.
    • All other laboratory test values <= Grade 1(Division of Acquired immune deficiency syndrome, National Institute of Health grading scale).
  7. Acceptable medical history, as assessed by the investigator, with chest X-ray and electrocardiogram within 1 year of study participation.
  8. Willingness to abstain from ingesting substances during the study which may alter plasma study drug levels by interaction with the cytochrome P450 system.
  9. A prior Acquired immune deficiency syndrome-defining event is acceptable as long as it has resolved or the patient has been on stable treatment for at least 2 months (Acquired immune deficiency syndrome related complex is acceptable).

Exclusion Criteria:

  1. Antiretroviral medication naïve.
  2. Patients on recent drug holiday, defined as off antiretroviral medications for at least 7 consecutive days within the last 3 months.
  3. Alanine aminotransferase >3x upper limit of normal and aspartate aminotransferase >2.5x upper limit of normal at either screening visit.
  4. Female patients of child-bearing potential who:

    • have a positive serum pregnancy test at screening or during the study,
    • are breast feeding
    • are planning to become pregnant, or
    • are not willing to use a barrier method of contraception, or
    • require ethinyl estradiol administration
  5. Prior tipranavir use.
  6. Use of investigational medications within 30 days before study entry or during the trial. (T-20 [enfuvirtide] and Tenofovir (Viread), investigational at the time of writing of this protocol, will be allowed.)
  7. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).
  8. Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator.
  9. In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Austria,   Belgium,   Brazil,   Denmark,   France,   Germany,   Greece,   Ireland,   Italy,   Mexico,   Netherlands,   Portugal,   Spain,   Sweden,   Switzerland,   United Kingdom
 
NCT00144170
1182.48, RESIST 2
Not Provided
Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
April 2014

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