Phase 3
N=866
Tipranavir/Ritonavir vs. Genotypically Defined Protease Inhibitor/Ritonavir in HIV Patients (RESIST-2)
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT00144170 ↗Enrolled (actual)
866
Serious AEs
24.5%
Results posted
Dec 2009
Primary outcome: Primary: Treatment Response at Week 48 — 34.5; 15 percentage of participants — p=0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tipranavir (with low dose ritonavir) (Drug); Comparator protease inhibitor(CPI)/low dose ritonavir(r) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Oct 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Treatment Response at Week 48 |
34.5; 15 | 0.0001 sig |
| PRIMARY Time to Treatment Failure Through 48 Weeks of Treatment |
112; 0 | 0.0001 sig |
| SECONDARY Treatment Response at Week 2 |
51; 25.9 | 0.0001 sig |
| SECONDARY Treatment Response at Week 4 |
59.1; 29.9 | 0.0001 sig |
| SECONDARY Treatment Response at Week 8 |
54.3; 24.5 | 0.0001 sig |
| SECONDARY Treatment Response at Week 16 |
47.1; 19.9 | 0.0001 sig |
| SECONDARY Treatment Response at Week 24 |
40.9; 18.0 | 0.0001 sig |
| SECONDARY Treatment Response at Week 32 |
37.2; 17.3 | 0.0001 sig |
| SECONDARY Treatment Response at Week 40 |
36.3; 16.6 | 0.0001 sig |
| SECONDARY Treatment Response at Week 56 |
32.6; 14.5 | 0.0001 sig |
| SECONDARY Treatment Response at Week 64 |
31; 13.3 | 0.0001 sig |
| SECONDARY Treatment Response at Week 72 |
30.1; 12.1 | 0.0001 sig |
| SECONDARY Treatment Response at Week 80 |
28.5; 11.4 | 0.0001 sig |
| SECONDARY Treatment Response at Week 88 |
27.8; 11 | 0.0001 sig |
| SECONDARY Treatment Response at Week 96 |
26.2; 10 | 0.0001 sig |
| SECONDARY Time to Treatment Failure Through 96 Weeks of Treatment |
115; 0 | 0.0001 sig |
| SECONDARY Time to Confirmed Virologic Failure Through 48 Weeks of Treatment |
117; 0 | 0.0001 sig |
| SECONDARY Time to Confirmed Virologic Failure Through 96 Weeks of Treatment |
117; 0 | 0.0001 sig |
| SECONDARY Virologic Response |
36.6; 16.8 | — |
| SECONDARY Virologic Response at Week 2 |
0.9; 1.4 | — |
| SECONDARY Virologic Response at Week 4 |
4.4; 3.5 | — |
| SECONDARY Virologic Response at Week 8 |
11; 6.8 | — |
| SECONDARY Virologic Response at Week 16 |
20.5; 10.5 | — |
| SECONDARY Virologic Response at Week 24 |
21.1; 11.9 | — |
| SECONDARY Virologic Response at Week 32 |
22.1; 12.1 | — |
| SECONDARY Virologic Response at Week 40 |
22.3; 11.9 | — |
| SECONDARY Virologic Response at Week 48 |
22.8; 10.5 | — |
| SECONDARY Virologic Response at Week 56 |
22.5; 8.9 | — |
| SECONDARY Virologic Response at Week 64 |
21.6; 8.2 | — |
| SECONDARY Virologic Response at Week 72 |
21.1; 8.2 | — |
| SECONDARY Virologic Response at Week 80 |
21.8; 8.9 | — |
| SECONDARY Virologic Response at Week 88 |
20.7; 8.9 | — |
| SECONDARY Virologic Response at Week 96 |
20; 8.9 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 2) |
-1.27; -0.56 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 4) |
-1.47; -0.42 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 8) |
-1.4; -0.33 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 16) |
-1.03; -0.3 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 24) |
-0.69; -0.21 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 32) |
-0.63; -0.24 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 40) |
-0.65; -0.2 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 48) |
-0.65; -0.2 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 56) |
-0.64; -0.22 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 64) |
-0.63; -0.21 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 72) |
-0.52; -0.2 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 80) |
-0.55; -0.2 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 88) |
-0.56; -0.2 | — |
| SECONDARY Median Change From Baseline in Viral Load (Week 96) |
-0.56; -0.2 | — |
| SECONDARY Virologic Response at Week 40 |
22.3; 11.9 | — |
| SECONDARY Virologic Response at Viral Load Nadir During Study Treatment Through 96 Weeks |
52.2; 25.7 | — |
| SECONDARY Virologic Response at Week 2 |
0.9; 1.4 | — |
| SECONDARY Virologic Response at Week 4 |
4.4; 3.5 | — |
| SECONDARY Virologic Response at Week 8 |
11; 6.8 | — |
| SECONDARY Virologic Response at Week 16 |
20.5; 10.5 | — |
| SECONDARY Virologic Response at Week 24 |
21.1; 11.9 | — |
| SECONDARY Virologic Response at Week 32 |
22.1; 12.1 | — |
| SECONDARY Virologic Response at Week 48 |
22.8; 10.5 | — |
| SECONDARY Virologic Response at Week 56 |
22.5; 8.9 | — |
| SECONDARY Virologic Response at Week 64 |
21.6; 8.2 | — |
| SECONDARY Virologic Response at Week 72 |
21.1; 8.2 | — |
| SECONDARY Virologic Response at Week 80 |
21.8; 8.9 | — |
| SECONDARY Virologic Response at Week 88 |
20.7; 8.9 | — |
| SECONDARY Virologic Response at Week 96 |
20; 8.9 | — |
| SECONDARY Virologic Response |
36.6; 16.8 | — |
| SECONDARY Virologic Response at Week 2 |
0.9; 1.4 | — |
| SECONDARY Virologic Response at Week 4 |
4.4; 3.5 | — |
| SECONDARY Virologic Response at Week 8 |
11; 6.8 | — |
| SECONDARY Virologic Response at Week 16 |
20.5; 10.5 | — |
| SECONDARY Virologic Response at Week 24 |
21.1; 11.9 | — |
| SECONDARY Virologic Response at Week 32 |
22.1; 12.1 | — |
| SECONDARY Virologic Response at Week 40 |
22.3; 11.9 | — |
| SECONDARY Virologic Response at Week 48 |
22.8; 10.5 | — |
| SECONDARY Virologic Response at Week 56 |
22.5; 8.9 | — |
| SECONDARY Virologic Response at Week 64 |
21.6; 8.2 | — |
| SECONDARY Virologic Response at Week 72 |
21.1; 8.2 | — |
| SECONDARY Virologic Response at Week 80 |
21.8; 8.9 | — |
| SECONDARY Virologic Response at Week 88 |
20.7; 8.9 | — |
| SECONDARY Virologic Response at Week 96 |
20; 8.9 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 2) |
26; 13 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 4) |
39; 19 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 8) |
52; 25 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 16) |
57; 25 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 24) |
51; 21 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 32) |
46; 17 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 40) |
47; 19 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 48) |
43; 16 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 56) |
39; 16 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 64) |
42; 13 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 72) |
42; 18 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 80) |
39; 19 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 88) |
41; 19 | — |
| SECONDARY Mean Change From Baseline in CD4+ Cell Count (Week 96) |
41; 20 | — |
| SECONDARY Time to New Centers for Disease Control (CDC) Class C Progression Event or Death. |
528; 332 | 0.1026 |
Summary
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.
Eligibility Criteria
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 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.
Data sourced from ClinicalTrials.gov (NCT00144170). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.