NCT00144170已完成3 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 882
- 试验地点
- 174
- 主要终点
- Treatment Response at Week 48
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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).
排除标准
- •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.
研究组 & 干预措施
Tipranavir(TPV)/low dose ritonavir(r)
Other
干预措施: Tipranavir (with low dose ritonavir) (Drug)
Comparator protease inhibitor(CPI)/low dose ritonavir(r)
Other
干预措施: Comparator protease inhibitor(CPI)/low dose ritonavir(r) (Drug)
结局指标
主要结局
Treatment Response at Week 48
时间窗: 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
Time to Treatment Failure Through 48 Weeks of Treatment
时间窗: 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.
次要结局
- Mean Change From Baseline in CD4+ Cell Count (Week 80)(Baseline to Week 80)
- Mean Change From Baseline in CD4+ Cell Count (Week 88)(Baseline to Week 88)
- Mean Change From Baseline in CD4+ Cell Count (Week 96)(Baseline to Week 96)
- Virologic Response at Week 56(Week 56)
- Mean Change From Baseline in CD4+ Cell Count (Week 48)(Baseline to Week 48)
- Mean Change From Baseline in CD4+ Cell Count (Week 56)(Baseline to Week 56)
- Treatment Response at Week 32(week 32)
- Treatment Response at Week 72(week 72)
- Mean Change From Baseline in CD4+ Cell Count (Week 64)(Baseline to Week 64)
- Treatment Response at Week 2(week 2)
- Treatment Response at Week 4(week 4)
- Treatment Response at Week 8(week 8)
- Treatment Response at Week 16(week 16)
- Treatment Response at Week 24(Week 24)
- Treatment Response at Week 40(week 40)
- Treatment Response at Week 56(week 56)
- Treatment Response at Week 64(week 64)
- Treatment Response at Week 80(week 80)
- Treatment Response at Week 88(week 88)
- Treatment Response at Week 96(after 96 weeks of treatment)
- Time to Treatment Failure Through 96 Weeks of Treatment(after 96 weeks of treatment)
- Time to Confirmed Virologic Failure Through 48 Weeks of Treatment(after 48 weeks of treatment)
- Time to Confirmed Virologic Failure Through 96 Weeks of Treatment(after 96 weeks of treatment)
- Virologic Response(Week 2 through Week 96 (at any point during trial))
- Virologic Response at Week 8(Week 8)
- Virologic Response at Week 2(Week 2)
- Virologic Response at Week 4(Week 4)
- Virologic Response at Week 48(Week 48)
- Virologic Response at Week 16(Week 16)
- Virologic Response at Week 24(Week 24)
- Virologic Response at Week 32(Week 32)
- Virologic Response at Week 40(Week 40)
- Mean Change From Baseline in CD4+ Cell Count (Week 72)(Baseline to Week 72)
- Virologic Response at Week 64(Week 64)
- Virologic Response at Week 72(Week 72)
- Virologic Response at Week 80(Week 80)
- Virologic Response at Week 88(Week 88)
- Virologic Response at Week 96(Week 96)
- Median Change From Baseline in Viral Load (Week 2)(Baseline to Week 2)
- Median Change From Baseline in Viral Load (Week 4)(Baseline to Week 4)
- Median Change From Baseline in Viral Load (Week 8)(Baseline to Week 8)
- Median Change From Baseline in Viral Load (Week 16)(Baseline to Week 16)
- Median Change From Baseline in Viral Load (Week 24)(Baseline to Week 24)
- Median Change From Baseline in Viral Load (Week 32)(Baseline to Week 32)
- Median Change From Baseline in Viral Load (Week 40)(Baseline to Week 40)
- Median Change From Baseline in Viral Load (Week 48)(Baseline to Week 48)
- Median Change From Baseline in Viral Load (Week 56)(Baseline to Week 56)
- Median Change From Baseline in Viral Load (Week 64)(Baseline to Week 64)
- Median Change From Baseline in Viral Load (Week 72)(Baseline to Week 72)
- Median Change From Baseline in Viral Load (Week 80)(Baseline to Week 80)
- Median Change From Baseline in Viral Load (Week 88)(Baseline to Week 88)
- Median Change From Baseline in Viral Load (Week 96)(Baseline to Week 96)
- Virologic Response at Viral Load Nadir During Study Treatment Through 96 Weeks(Week 2 through Week 96 (at any point during trial))
- Mean Change From Baseline in CD4+ Cell Count (Week 2)(Baseline to Week 2)
- Mean Change From Baseline in CD4+ Cell Count (Week 4)(Baseline to Week 4)
- Mean Change From Baseline in CD4+ Cell Count (Week 8)(Baseline to Week 8)
- Mean Change From Baseline in CD4+ Cell Count (Week 16)(Baseline to Week 16)
- Mean Change From Baseline in CD4+ Cell Count (Week 24)(Baseline to Week 24)
- Mean Change From Baseline in CD4+ Cell Count (Week 32)(Baseline to Week 32)
- Mean Change From Baseline in CD4+ Cell Count (Week 40)(Baseline to Week 40)
- Time to New Centers for Disease Control (CDC) Class C Progression Event or Death.(up to 75 weeks of treatment)
研究者
研究点 (174)
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