Randomized Evaluation of Strategic Intervention in Multidrug Resistant Patients With Tipranavir (RESIST)

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00054717
First received: February 7, 2003
Last updated: June 23, 2014
Last verified: April 2014
  Purpose

Demonstrate the safety and efficacy of Tipranavir/Ritonavir versus an active treatment regimen in highly treatment experienced Human Immunodeficiency virus 1(HIV-1) infected patients.


Condition Intervention Phase
HIV Infections
Drug: Tipranavir
Drug: Ritonavir(r)
Drug: Comparator Protease Inhibitor (CPI)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Randomized, Open-label, Comparative Safety and Efficacy Study of Tipranavir Boosted With Low-dose Ritonavir (TPV/RTV) Verses Genotypically-defined Protease Inhibitor/Ritonavir (PI/RTV) in Multiple Antiretroviral Drug-experienced Patients.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Treatment Response at Week 48 [ Time Frame: At week 48 ] [ Designated as safety issue: No ]
    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: Week 48 ] [ 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 VL measurements <1 log10 below baseline.


Secondary Outcome Measures:
  • Treatment Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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 2 [ Time Frame: week 2 ] [ Designated as safety issue: No ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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: Week 96 ] [ Designated as safety issue: No ]
    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: Week 96 ] [ 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 VL measurements <1 log10 below baseline.

  • Time to Confirmed Virologic Failure Through 48 Weeks of Treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Time to virologic failure is defined as the time from the start of treatment to the last measurement with a viral load reduction greater than 1.0 log before a confirmed drop of viral load reduction below 1.0 log.

  • Time to Confirmed Virologic Failure Through 96 Weeks of Treatment [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Time to virologic failure is defined as the time from the start of treatment to the last measurement with a viral load reduction greater than 1.0 log before a confirmed drop of viral load reduction below 1.0 log.

  • Virologic Response (Viral Load >= 1 Log Drop) at Viral Load Nadir, LOCF [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 40 [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Virologic Response (Viral Load >= 1 Log Drop) at Week 64 [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load (VL) >= 1 log reduction from baseline

  • Median Change From Baseline in Viral Load to Week 2 [ Time Frame: Baseline to Week 2 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 4 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 16 [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 32 [ Time Frame: Baseline to Week 32 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 40 [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 56 [ Time Frame: Baseline to Week 56 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 64 [ Time Frame: Baseline to Week 64 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 72 [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 80 [ Time Frame: Baseline to Week 80 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 88 [ Time Frame: Baseline to Week 88 ] [ Designated as safety issue: No ]
  • Median Change From Baseline in Viral Load to Week 96 [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 2 in CD4+ Cell Count [ Time Frame: Baseline to Week 2 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 4 in CD4+ Cell Count [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 8 in CD4+ Cell Count [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 16 in CD4+ Cell Count [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 24 in CD4+ Cell Count [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 32 in CD4+ Cell Count [ Time Frame: Baseline to Week 32 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 40 in CD4+ Cell Count [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 48 in CD4+ Cell Count [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 56 in CD4+ Cell Count [ Time Frame: Baseline to Week 56 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 64 in CD4+ Cell Count [ Time Frame: Baseline to Week 64 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 72 in CD4+ Cell Count [ Time Frame: Baseline to Week 72 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 80 in CD4+ Cell Count [ Time Frame: Baseline to Week 80 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 88 in CD4+ Cell Count [ Time Frame: Baseline to Week 88 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline to Week 96 in CD4+ Cell Count [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Time to New CDC Class C Progression Event or Death. [ Time Frame: after 48 weeks of treatment ] [ Designated as safety issue: No ]
    Time to new Centers for Disease Control and Prevention (CDC) class C progression event (i.e., new AIDS defining illness) or death

  • Virologic Response (VL < 400 Copies/ml) at Viral Load Nadir, LOCF [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 32 [ Time Frame: week 32 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 40 [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 64 [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 80 [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 88 [ Time Frame: week 88 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 400 Copies/ml) at Week 96 [ Time Frame: week 96 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 400 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Viral Load Nadir, LOCF [ Time Frame: Week 2 through Week 96 (at any point during trial) ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 40 [ Time Frame: Week 40 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 64 [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 80 [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 88 [ Time Frame: Week 88 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Virologic Response (VL < 50 Copies/ml) at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    Percentage of participants with Viral Load < 50 copies/mL

  • Percentage of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 Laboratory Abnormalities [ Time Frame: 240 Weeks ] [ Designated as safety issue: No ]
    NIH Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.


Enrollment: 630
Study Start Date: January 2003
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Tipranavir(TPV)/low dose ritonavir(r) Drug: Tipranavir Drug: Ritonavir(r)
Comparator protease inhibitor(CPI)/low dose ritonavir(r) Drug: Ritonavir(r) Drug: Comparator Protease Inhibitor (CPI)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients meeting the following criteria will be eligible for participation in th is study:

  1. Human Immunodeficiency virus 1 (HIV-1) infected males or females >=18 years of age.
  2. Screening genotypic resistance report indicating both of the following: at least one primary protease Inhibitor (PI) 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.

3. At least 3 consecutive months experience taking antiretrovirals (ARVs) from each of the classes of nucleoside reverse transcriptase inhibitors(NRTI(s)), non-nucleoside reverse transcriptase inhibitors(NNRTI(s)), and protease inhibitors (PIs) at some point in treatment history,with at least 2 protease inhibitor (PI)-based regimens, one of which must be the current regimen, and current protease inhibitor (PI)-based antiretroviral (ARV) medication regimen for at least 3 months prior to randomization.

4. Human Immunodeficiency Virus 1 (HIV-1) viral load >=1,000 copies/mL at screening.

Exclusion criteria:

Patients with any of the following criteria are excluded from participation in t he study:

  1. Antiretroviral (ARV) medication naïve.
  2. Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the last 3 months.
  3. alanine aminotransferase (ALT) >=3.0x upper limit of normal (ULN) and aspartate aminotransferase(AST) >=2.5x upper limit of normal (ULN) (>=Division of AIDS(DAIDS) Grade 1) at either screening visit.
  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: NCT00054717

  Show 117 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00054717     History of Changes
Other Study ID Numbers: 1182.12
Study First Received: February 7, 2003
Results First Received: September 9, 2009
Last Updated: June 23, 2014
Health Authority: Australia: Responsilble Ethics Committee
Canada: Health Canada (TPD)
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 22, 2014