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Completed

NCT Number: NCT00144170

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

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.

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

1182.48.5401 Fundación Huésped, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed informed consent prior to trial participation.
  • Human immunodeficiency virus-1 infected males or females >=18 years of age.
  • 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.
  • 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.
  • Human immunodeficiency virus-1 viral load >=1000 copies/mL at screening.
  • 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).
  • Acceptable medical history, as assessed by the investigator, with chest X-ray and electrocardiogram within 1 year of study participation.
  • Willingness to abstain from ingesting substances during the study which may alter plasma study drug levels by interaction with the cytochrome P450 system.
  • 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

  • Antiretroviral medication naïve.
  • Patients on recent drug holiday, defined as off antiretroviral medications for at least 7 consecutive days within the last 3 months.
  • Alanine aminotransferase >3x upper limit of normal and aspartate aminotransferase >2.5x upper limit of normal at either screening visit.
  • 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
  • Prior tipranavir use.
  • 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.)
  • Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g. interferon, cyclosporin, hydroxyurea, interleukin 2).
  • Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator.
  • In the opinion of the investigator, likely survival of less than 12 months because of underlying disease.

Treatment and study plan

Tipranavir (with low dose ritonavir)

Drug

Comparator protease inhibitor(CPI)/low dose ritonavir(r)

Drug

Primary outcomes

  1. Treatment Response at Week 48

    Time frame: after 48 weeks of treatment

    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

  2. Time to Treatment Failure Through 48 Weeks of Treatment

    Time frame: after 48 weeks of treatment

    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.

Secondary outcomes

  1. Treatment Response at Week 2

    Time frame: week 2

    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

  2. Treatment Response at Week 4

    Time frame: week 4

    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

  3. Treatment Response at Week 8

    Time frame: week 8

    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

  4. Treatment Response at Week 16

    Time frame: week 16

    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

  5. Treatment Response at Week 24

    Time frame: Week 24

    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

  6. Treatment Response at Week 32

    Time frame: week 32

    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

  7. Treatment Response at Week 40

    Time frame: week 40

    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

  8. Treatment Response at Week 56

    Time frame: week 56

    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

  9. Treatment Response at Week 64

    Time frame: week 64

    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

  10. Treatment Response at Week 72

    Time frame: week 72

    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

  11. Treatment Response at Week 80

    Time frame: week 80

    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

  12. Treatment Response at Week 88

    Time frame: week 88

    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

  13. Treatment Response at Week 96

    Time frame: after 96 weeks of treatment

    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

  14. Time to Treatment Failure Through 96 Weeks of Treatment

    Time frame: after 96 weeks of treatment

    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.

  15. Time to Confirmed Virologic Failure Through 48 Weeks of Treatment

    Time frame: after 48 weeks of treatment

    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.

  16. Time to Confirmed Virologic Failure Through 96 Weeks of Treatment

    Time frame: after 96 weeks of treatment

    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.

  17. Virologic Response

    Time frame: Week 2 through Week 96 (at any point during trial)

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  18. Virologic Response at Week 2

    Time frame: Week 2

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  19. Virologic Response at Week 4

    Time frame: week 4

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  20. Virologic Response at Week 8

    Time frame: week 8

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  21. Virologic Response at Week 16

    Time frame: week 16

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  22. Virologic Response at Week 24

    Time frame: week 24

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  23. Virologic Response at Week 32

    Time frame: week 32

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  24. Virologic Response at Week 40

    Time frame: week 40

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  25. Virologic Response at Week 48

    Time frame: week 48

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  26. Virologic Response at Week 56

    Time frame: week 56

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  27. Virologic Response at Week 64

    Time frame: week 64

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  28. Virologic Response at Week 72

    Time frame: Week 72

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  29. Virologic Response at Week 80

    Time frame: Week 80

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  30. Virologic Response at Week 88

    Time frame: Week 88

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  31. Virologic Response at Week 96

    Time frame: Week 96

    Virologic response is defined as: Log(baseline viral load (VL))-Log(on-treatment VL)>=1

  32. Median Change From Baseline in Viral Load (Week 2)

    Time frame: Baseline to Week 2

  33. Median Change From Baseline in Viral Load (Week 4)

    Time frame: Baseline to Week 4

  34. Median Change From Baseline in Viral Load (Week 8)

    Time frame: Baseline to Week 8

  35. Median Change From Baseline in Viral Load (Week 16)

    Time frame: Baseline to Week 16

  36. Median Change From Baseline in Viral Load (Week 24)

    Time frame: Baseline to Week 24

  37. Median Change From Baseline in Viral Load (Week 32)

    Time frame: Baseline to Week 32

  38. Median Change From Baseline in Viral Load (Week 40)

    Time frame: Baseline to Week 40

  39. Median Change From Baseline in Viral Load (Week 48)

    Time frame: Baseline to Week 48

  40. Median Change From Baseline in Viral Load (Week 56)

    Time frame: Baseline to Week 56

  41. Median Change From Baseline in Viral Load (Week 64)

    Time frame: Baseline to Week 64

  42. Median Change From Baseline in Viral Load (Week 72)

    Time frame: Baseline to Week 72

  43. Median Change From Baseline in Viral Load (Week 80)

    Time frame: Baseline to Week 80

  44. Median Change From Baseline in Viral Load (Week 88)

    Time frame: Baseline to Week 88

  45. Median Change From Baseline in Viral Load (Week 96)

    Time frame: Baseline to Week 96

  46. Virologic Response at Week 40

    Time frame: Week 40

    Virologic response defined as Viral Load<400 copies/mL

  47. Virologic Response at Viral Load Nadir During Study Treatment Through 96 Weeks

    Time frame: Week 2 through Week 96 (at any point during trial)

    Virologic response defined as Viral Load<400 copies/mL

  48. Virologic Response at Week 2

    Time frame: Week 2

    Virologic response defined as Viral Load<400 copies/mL

  49. Virologic Response at Week 4

    Time frame: Week 4

    Virologic response defined as Viral Load<400 copies/mL

  50. Virologic Response at Week 8

    Time frame: Week 8

    Virologic response defined as Viral Load<400 copies/mL

  51. Virologic Response at Week 16

    Time frame: Week 16

    Virologic response defined as Viral Load<400 copies/mL

  52. Virologic Response at Week 24

    Time frame: Week 24

    Virologic response defined as Viral Load<400 copies/mL

  53. Virologic Response at Week 32

    Time frame: Week 32

    Virologic response defined as Viral Load<400 copies/mL

  54. Virologic Response at Week 48

    Time frame: Week 48

    Virologic response defined as Viral Load<400 copies/mL

  55. Virologic Response at Week 56

    Time frame: Week 56

    Virologic response defined as Viral Load<400 copies/mL

  56. Virologic Response at Week 64

    Time frame: Week 64

    Virologic response defined as Viral Load<400 copies/mL

  57. Virologic Response at Week 72

    Time frame: Week 72

    Virologic response defined as Viral Load<400 copies/mL

  58. Virologic Response at Week 80

    Time frame: Week 80

    Virologic response defined as Viral Load<400 copies/mL

  59. Virologic Response at Week 88

    Time frame: week 88

    Virologic response defined as Viral Load<400 copies/mL

  60. Virologic Response at Week 96

    Time frame: week 96

    Virologic response defined as Viral Load<400 copies/mL

  61. Virologic Response

    Time frame: Week 2 through Week 96 (at any point during trial)

    Virologic response defined as Viral Load<50 copies/mL

  62. Virologic Response at Week 2

    Time frame: Week 2

    Virologic response defined as Viral Load<50 copies/mL

  63. Virologic Response at Week 4

    Time frame: Week 4

    Virologic response defined as Viral Load<50 copies/mL

  64. Virologic Response at Week 8

    Time frame: Week 8

    Virologic response defined as Viral Load<50 copies/mL

  65. Virologic Response at Week 16

    Time frame: Week 16

    Virologic response defined as Viral Load<50 copies/mL

  66. Virologic Response at Week 24

    Time frame: Week 24

    Viral Load < 50 copies/mL

  67. Virologic Response at Week 32

    Time frame: Week 32

    Virologic response defined as Viral Load<50 copies/mL

  68. Virologic Response at Week 40

    Time frame: Week 40

    Virologic response defined as Viral Load<50 copies/mL

  69. Virologic Response at Week 48

    Time frame: Week 48

    Virologic response defined as Viral Load<50 copies/mL

  70. Virologic Response at Week 56

    Time frame: Week 56

    Virologic response defined as Viral Load<50 copies/mL

  71. Virologic Response at Week 64

    Time frame: Week 64

    Virologic response defined as Viral Load<50 copies/mL

  72. Virologic Response at Week 72

    Time frame: Week 72

    Virologic response defined as Viral Load<50 copies/mL

  73. Virologic Response at Week 80

    Time frame: Week 80

    Virologic response defined as Viral Load<50 copies/mL

  74. Virologic Response at Week 88

    Time frame: Week 88

    Virologic response defined as Viral Load<50 copies/mL

  75. Virologic Response at Week 96

    Time frame: Week 96

    Virologic response defined as Viral Load<50 copies/mL

  76. Mean Change From Baseline in CD4+ Cell Count (Week 2)

    Time frame: Baseline to Week 2

  77. Mean Change From Baseline in CD4+ Cell Count (Week 4)

    Time frame: Baseline to Week 4

  78. Mean Change From Baseline in CD4+ Cell Count (Week 8)

    Time frame: Baseline to Week 8

  79. Mean Change From Baseline in CD4+ Cell Count (Week 16)

    Time frame: Baseline to Week 16

  80. Mean Change From Baseline in CD4+ Cell Count (Week 24)

    Time frame: Baseline to Week 24

  81. Mean Change From Baseline in CD4+ Cell Count (Week 32)

    Time frame: Baseline to Week 32

  82. Mean Change From Baseline in CD4+ Cell Count (Week 40)

    Time frame: Baseline to Week 40

  83. Mean Change From Baseline in CD4+ Cell Count (Week 48)

    Time frame: Baseline to Week 48

  84. Mean Change From Baseline in CD4+ Cell Count (Week 56)

    Time frame: Baseline to Week 56

  85. Mean Change From Baseline in CD4+ Cell Count (Week 64)

    Time frame: Baseline to Week 64

  86. Mean Change From Baseline in CD4+ Cell Count (Week 72)

    Time frame: Baseline to Week 72

  87. Mean Change From Baseline in CD4+ Cell Count (Week 80)

    Time frame: Baseline to Week 80

  88. Mean Change From Baseline in CD4+ Cell Count (Week 88)

    Time frame: Baseline to Week 88

  89. Mean Change From Baseline in CD4+ Cell Count (Week 96)

    Time frame: Baseline to Week 96

  90. Time to New Centers for Disease Control (CDC) Class C Progression Event or Death.

    Time frame: up to 75 weeks of treatment

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

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)

Important dates

Study start
2003
Primary completion
2008
First posted
Sep 5, 2005
Registry last updated
Jul 2, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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