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

NCT00144170 | Completed Phase 3 Results

• 2 other identifiers: 1182.48RESIST 2
• Study Type: interventional
• Target: 882
• Locations: 17 countries
• Sites: 174

Brief 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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Treatment Response at Week 48

  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

  after 48 weeks of treatment

• Time to Treatment Failure Through 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.

  after 48 weeks of treatment

Secondary Outcomes (90)

• 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

Study Arms (2)

Tipranavir(TPV)/low dose ritonavir(r)

OTHER

Drug: Tipranavir (with low dose ritonavir)

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

OTHER

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

Interventions

Tipranavir (with low dose ritonavir) DRUG

Tipranavir(TPV)/low dose ritonavir(r)

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (174)

1182.48.5401 Fundación Huésped

Buenos Aires, Argentina

Location

1182.48.5402 Fundación Huésped

Buenos Aires, Argentina

Location

1182.48.5403 Servicio de Infecciosas

Buenos Aires, Argentina

Location

1182.48.5404 Servicio de Infecciosas

Buenos Aires, Argentina

Location

1182.48.5405 Hospital Muniz

Buenos Aires, Argentina

Location

1182.48.5406 Servicio de Immunocomprometido

Buenos Aires, Argentina

Location

1182.48.4301 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1182.48.3209 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Location

1182.48.3201 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1182.48.3202 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1182.48.3206 Boehringer Ingelheim Investigational Site

Charleroi, Belgium

Location

1182.48.3207 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

1182.48.3210 Boehringer Ingelheim Investigational Site

Luxembourg, Belgium

Location

1182.48.5512 Cidade Universitária Zeferino Vaz-Clínica Médica FCM

Campinas - SP, Brazil

Location

1182.48.5505 Instituto A-Z de Pesquisa e Ensino da PUC

Curitiba - PR, Brazil

Location

1182.48.5507 Hospital Geral de Nova Iguaçu - Ministério da Saúde

Nova Iguaçu - RJ, Brazil

Location

1182.48.5502 Fundação Oswaldo Cruz

Rio de Janeiro - RJ, Brazil

Location

1182.48.5509 Universidade Federal do Rio de Janeiro

Rio de Janeiro - RJ, Brazil

Location

1182.48.5511 Universidade Federal da Bahia-Unidade Docente Assistencial d

Salvador - BA, Brazil

Location

1182.48.5501 Clínica de Doenças Parasitárias e Infecciosas-Hospital Dia

São Paulo - SP, Brazil

Location

1182.48.5503 I.I. Emilio Ribas - Moléstias Infecciosas

São Paulo - SP, Brazil

Location

1182.48.5504 Hospital do Servidor Público Estadual - IAMSPE

São Paulo - SP, Brazil

Location

1182.48.5506 Centro de Referência e Treinamento - DST/AIDS

São Paulo - SP, Brazil

Location

1182.48.5508 I.I. Emilio Ribas

São Paulo - SP, Brazil

Location

1182.48.5510 INCOR e Hospital das Clínicas da Universidade de São Paulo

São Paulo - SP, Brazil

Location

1182.48.5513 UNIFESP - Centro de Pesquisa Clinica

São Paulo - SP, Brazil

Location

1182.48.4505 Boehringer Ingelheim Investigational Site

Aarhus N, Denmark

Location

1182.48.4502 Boehringer Ingelheim Investigational Site

Hvidovre, Denmark

Location

1182.48.4501 Boehringer Ingelheim Investigational Site

København Ø, Denmark

Location

1182.48.4504 Boehringer Ingelheim Investigational Site

Odense C, Denmark

Location

1182.48.3311 Boehringer Ingelheim Investigational Site

Besançon, France

Location

1182.48.3307 Boehringer Ingelheim Investigational Site

Bordeaux, France

Location

1182.48.3317 Boehringer Ingelheim Investigational Site

Bordeaux, France

Location

1182.48.3302 Boehringer Ingelheim Investigational Site

Caen, France

Location

1182.48.3303 Boehringer Ingelheim Investigational Site

Clamart, France

Location

1182.48.3305 Boehringer Ingelheim Investigational Site

Le Kremlin-Bicêtre, France

Location

1182.48.3304 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1182.48.3322 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1182.48.3308 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1182.48.3309 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1182.48.3318 Boehringer Ingelheim Investigational Site

Nantes, France

Location

1182.48.3306 Boehringer Ingelheim Investigational Site

Nice, France

Location

1182.48.3301 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3310 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3312 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3316 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3319 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3321 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3323 Boehringer Ingelheim Investigational Site

Paris, France

Location

1182.48.3315 Boehringer Ingelheim Investigational Site

Rennes, France

Location

1182.48.3313 Boehringer Ingelheim Investigational Site

Strasbourg, France

Location

1182.48.3314 Boehringer Ingelheim Investigational Site

Vandœuvre-lès-Nancy, France

Location

1182.48.3320 Boehringer Ingelheim Investigational Site

Villejuif, France

Location

1182.48.4911 Boehringer Ingelheim Investigational Site

Aachen, Germany

Location

1182.48.4901 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1182.48.4902 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1182.48.4903 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

1182.48.4918 Boehringer Ingelheim Investigational Site

Bonn, Germany

Location

1182.48.4905 Boehringer Ingelheim Investigational Site

Cologne, Germany

Location

1182.48.4926 Boehringer Ingelheim Investigational Site

Cologne, Germany

Location

1182.48.4906 Boehringer Ingelheim Investigational Site

Dortmund, Germany

Location

1182.48.4912 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1182.48.4914 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1182.48.4908 Boehringer Ingelheim Investigational Site

Erlangen, Germany

Location

1182.48.4904 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1182.48.4924 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1182.48.4928 Boehringer Ingelheim Investigational Site

Freiburg im Breisgau, Germany

Location

1182.48.4930 Boehringer Ingelheim Investigational Site

Freiburg/Breisgau, Germany

Location

1182.48.4916 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1182.48.4929 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1182.48.4931 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1182.48.4913 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1182.48.4920 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1182.48.4909 Boehringer Ingelheim Investigational Site

Heidelberg, Germany

Location

1182.48.4923 Boehringer Ingelheim Investigational Site

Mannheim, Germany

Location

1182.48.4907 Boehringer Ingelheim Investigational Site

München, Germany

Location

1182.48.4910 Boehringer Ingelheim Investigational Site

München, Germany

Location

1182.48.4915 Boehringer Ingelheim Investigational Site

Osnabrück, Germany

Location

1182.48.4919 Boehringer Ingelheim Investigational Site

Regensburg, Germany

Location

1182.48.4921 Boehringer Ingelheim Investigational Site

Stuttgart, Germany

Location

1182.48.4927 Boehringer Ingelheim Investigational Site

Stuttgart, Germany

Location

1182.48.3001 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1182.48.3002 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1182.48.3003 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1182.48.3004 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1182.48.3006 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1182.48.3007 Boehringer Ingelheim Investigational Site

Athens, Greece

Location

1182.48.3005 Boehringer Ingelheim Investigational Site

Goudi, Athens, Greece

Location

1182.48.3010 Boehringer Ingelheim Investigational Site

Pátrai, Greece

Location

1182.48.3008 Boehringer Ingelheim Investigational Site

Peraeus, Greece

Location

1182.48.3009 Boehringer Ingelheim Investigational Site

Thessaloniki, Greece

Location

1182.48.3531 Boehringer Ingelheim Investigational Site

Dublin, Ireland

Location

1182.48.3930 Boehringer Ingelheim Investigational Site

Ancona, Italy

Location

1182.48.3920 Boehringer Ingelheim Investigational Site

Antella (fi), Italy

Location

1182.48.3926 Boehringer Ingelheim Investigational Site

Bari, Italy

Location

1182.48.3932 Boehringer Ingelheim Investigational Site

Bergamo, Italy

Location

1182.48.3908 Boehringer Ingelheim Investigational Site

Brescia, Italy

Location

1182.48.3929 Boehringer Ingelheim Investigational Site

Busto Arsizio (va), Italy

Location

1182.48.3917 Boehringer Ingelheim Investigational Site

Ferrara, Italy

Location

1182.48.3919 Boehringer Ingelheim Investigational Site

Florence, Italy

Location

1182.48.3905 Boehringer Ingelheim Investigational Site

Genova, Italy

Location

1182.48.3927 Boehringer Ingelheim Investigational Site

Genova, Italy

Location

1182.48.3925 Boehringer Ingelheim Investigational Site

Lecco, Italy

Location

1182.48.3910 Boehringer Ingelheim Investigational Site

Macerata, Italy

Location

1182.48.3901 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.48.3907 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.48.3924 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.48.3934 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1182.48.3915 Boehringer Ingelheim Investigational Site

Modena, Italy

Location

1182.48.3912 Boehringer Ingelheim Investigational Site

Napoli, Italy

Location

1182.48.3921 Boehringer Ingelheim Investigational Site

Padua, Italy

Location

1182.48.3916 Boehringer Ingelheim Investigational Site

Pavia, Italy

Location

1182.48.3922 Boehringer Ingelheim Investigational Site

Pavia, Italy

Location

1182.48.3904 Boehringer Ingelheim Investigational Site

Rimini, Italy

Location

1182.48.3902 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1182.48.3903 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1182.48.3909 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1182.48.3935 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1182.48.3906 Boehringer Ingelheim Investigational Site

Torino, Italy

Location

1182.48.3914 Boehringer Ingelheim Investigational Site

Torino, Italy

Location

1182.48.3931 Boehringer Ingelheim Investigational Site

Torino, Italy

Location

1182.48.3933 Boehringer Ingelheim Investigational Site

Treviso, Italy

Location

1182.48.5201 Centro Médico La Raza IMSS

Mexico City, Mexico

Location

1182.48.5202 Hospital Lopez Mateos

México, Mexico

Location

1182.48.5203 Centro Guadalajara, Jal.

México, Mexico

Location

1182.48.5206 Centro Medico San Vicente

Monterrey, N.l., Mexico

Location

1182.48.3101 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

Location

1182.48.3106 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

Location

1182.48.3108 Boehringer Ingelheim Investigational Site

Groningen, Netherlands

Location

1182.48.3105 Boehringer Ingelheim Investigational Site

Nijmegen, Netherlands

Location

1182.48.3104 Boehringer Ingelheim Investigational Site

Rotterdam, Netherlands

Location

1182.48.3110 Boehringer Ingelheim Investigational Site

The Hague, Netherlands

Location

1182.48.3502 Boehringer Ingelheim Investigational Site

Cascais, Portugal

Location

1182.48.3503 Boehringer Ingelheim Investigational Site

Coimbra, Portugal

Location

1182.48.3501 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1182.48.3505 Hospital Egas Moniz

Lisbon, Portugal

Location

1182.48.3504 Hospital de São João

Porto, Portugal

Location

1182.48.3415 Boehringer Ingelheim Investigational Site

Alicante, Spain

Location

1182.48.3405 Boehringer Ingelheim Investigational Site

Badalona, Spain

Location

1182.48.3401 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1182.48.3407 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1182.48.3408 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1182.48.3409 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1182.48.3416 Boehringer Ingelheim Investigational Site

Donostia / San Sebastian, Spain

Location

1182.48.3406 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1182.48.3402 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1182.48.3403 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1182.48.3404 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1182.48.3410 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1182.48.3411 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1182.48.3412 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1182.48.3417 Boehringer Ingelheim Investigational Site

Málaga, Spain

Location

1182.48.3413 Boehringer Ingelheim Investigational Site

Seville, Spain

Location

1182.48.3414 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1182.48.3420 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1182.48.3418 Boehringer Ingelheim Investigational Site

Vigo, Spain

Location

1182.48.4603 Boehringer Ingelheim Investigational Site

Gothenburg, Sweden

Location

1182.48.4602 Boehringer Ingelheim Investigational Site

Malmo, Sweden

Location

1182.48.4601 Boehringer Ingelheim Investigational Site

Stockholm, Sweden

Location

1182.48.4101 Universitätsspital Basel

Basel, Switzerland

Location

1182.48.4104 Hopital Universitaire de Genève

Geneva, Switzerland

Location

1182.48.4103 Kantonsspital St. Gallen

Sankt Gallen, Switzerland

Location

1182.48.4102 Universitätsspital Zürich

Zurich, Switzerland

Location

1182.48.4405 Boehringer Ingelheim Investigational Site

Brighton, United Kingdom

Location

1182.48.4412 Boehringer Ingelheim Investigational Site

Edinburgh, United Kingdom

Location

1182.48.4411 Boehringer Ingelheim Investigational Site

Liverpool, United Kingdom

Location

1182.48.4404 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1182.48.4406 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1182.48.4408 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1182.48.4409 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1182.48.4414 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1182.48.4418 Boehringer Ingelheim Investigational Site

London, United Kingdom

Location

1182.48.4417 Boehringer Ingelheim Investigational Site

Newcastle upon Tyne, United Kingdom

Location

1182.48.4407 Boehringer Ingelheim Investigational Site

Portsmouth, United Kingdom

Location

Related Publications (2)

• Mikl J, Sulkowski MS, Benhamou Y, Dieterich D, Pol S, Rockstroh J, Robinson PA, Ranga M, Stern JO. Hepatic profile analyses of tipranavir in Phase II and III clinical trials. BMC Infect Dis. 2009 Dec 14;9:203. doi: 10.1186/1471-2334-9-203.

  PMID: 20003457 DERIVED

• Hicks CB, Cahn P, Cooper DA, Walmsley SL, Katlama C, Clotet B, Lazzarin A, Johnson MA, Neubacher D, Mayers D, Valdez H; RESIST investigator group. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet. 2006 Aug 5;368(9534):466-75. doi: 10.1016/S0140-6736(06)69154-X.

  PMID: 16890833 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

tipranavir; Ritonavir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 5, 2005
• Study Start: February 1, 2003
• Primary Completion: October 1, 2008
• Last Updated: July 2, 2014
• Results First Posted: December 23, 2009

Record last verified: 2014-04

Locations

PT (5); SE (3); IT (30); BR (13); GB (11); AR (6); CH (4); IE (1); NL (6); AU (1); FR (23); BE (6); ES (19); DK (4); DE (28); ME (4); GR (10)