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A Randomized Trial of the Efficacy and Safety of a Strategy of Starting With Nelfinavir Versus Ritonavir Added to Background Antiretroviral (AR) Nucleoside Therapy in HIV-Infected Individuals With CD4+ Cell Counts Less Than or Equal to 200/mm3

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000859
First received: November 2, 1999
Last updated: September 28, 2013
Last verified: September 2013
  Purpose

To compare nelfinavir (NFV) with ritonavir (RTV) for delaying disease progression or death in HIV-infected patients with CD4+ cell counts less than 100 cells/mm3 [AS PER AMENDMENT 3/11/98: less than or equal to 200 cells/mm3]. To compare NFV with RTV for the development of adverse events and for rates of permanent discontinuation of study medication.

[AS PER AMENDMENT 10/02/97: To compare by intention-to-treat analysis for disease progression, including death, the following two regimens: NFV plus background combination antiretroviral (AR) therapy followed by indinavir (IDV) or RTV in the event of significant intolerance; and RTV plus AR therapy followed by IDV, then NFV, in the event of significant intolerance.] [AS PER AMENDMENT 3/11/98: SUBSTUDY CPCRA 045: To determine the relative rates of emergence of HIV-1 resistance and to compare changes in plasma HIV RNA levels and CD4+ cell counts in a sample of patients with CD4+ cell counts <= 200/mm3 who are enrolled in protocol CPCRA 042.] AR therapy is rapidly becoming the standard of care for the treatment of HIV infection. AR therapy provides the best opportunity for maximizing viral suppression, reducing toxicity and delaying the emergence of resistant strains. The newest class of AR agents, the HIV protease inhibitors, exhibits the most potent anti-HIV effects described to date. This study will compare 2 protease inhibitors, NFV and RTV for efficacy and safety in a population with advanced HIV disease, who are taking various background nucleoside therapies.


Condition Intervention
HIV Infections
Drug: Indinavir sulfate
Drug: Ritonavir
Drug: Nelfinavir mesylate

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Randomized Trial of the Efficacy and Safety of a Strategy of Starting With Nelfinavir Versus Ritonavir Added to Background Antiretroviral (AR) Nucleoside Therapy in HIV-Infected Individuals With CD4+ Cell Counts Less Than or Equal to 200/mm3

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 1300
Study Completion Date: December 2001
Detailed Description:

AR therapy is rapidly becoming the standard of care for the treatment of HIV infection. AR therapy provides the best opportunity for maximizing viral suppression, reducing toxicity and delaying the emergence of resistant strains. The newest class of AR agents, the HIV protease inhibitors, exhibits the most potent anti-HIV effects described to date. This study will compare 2 protease inhibitors, NFV and RTV for efficacy and safety in a population with advanced HIV disease, who are taking various background nucleoside therapies.

Eligible patients will be randomized either to NFV plus background AR nucleoside therapy or to RTV plus background AR nucleoside therapy. Background AR therapy may also be no background therapy, although use of protease inhibitors as monotherapy is not recommended unless there is no alternative. Patients will be allowed to cross over to the alternate protease inhibitor if they reach a primary study endpoint. Data will be collected every 4 months.

[AS PER AMENDMENT 10/2/97: Patients assigned to the NFV arm who develop a significant intolerance may switch to RTV or IDV; those assigned to the RTV arm who develop a significant intolerance are encouraged to switch to IDV (NFV allowed if IDV contraindicated). Switchover for intolerance is strongly discouraged during the first 4 weeks of follow-up. Patients initially assigned to NFV therapy who experience disease progression may switch to RTV; if RTV is not tolerated, patients may switch to IDV. Because of the cross-resistance between RTV and IDV, patients who progress on RTV should switch to NFV.] [AS PER AMENDMENT 12/15/98: Patients originally assigned to NFV who experience poor virologic control or disease progression should change to RTV or IDV or enroll in the PIP protocol (CPCRA 057). Conversely, patients originally assigned to RTV should change to NFV or enroll in the PIP protocol (such patients continue to be followed on this study). Because of cross-resistance between RTV and IDV, change from RTV to IDV is discouraged. Determination of poor virologic control or disease progression is at the discretion of the patient's clinician. Change in background antiretroviral therapy should occur at the same time that the protease inhibitor is changed for poor virologic control or progression; the choice of new background antiretroviral agents is at the discretion of the clinician.] Randomization is stratified by clinical site.] [AS PER AMENDMENT 3/11/98: SUBSTUDY CPCRA 045: At least 600 patients (>= 400 from CPCRA sites and >= 200 from CTN sites) will be enrolled in the substudy. These patients will have a plasma sample collected for HIV RNA and genotypic resistance within 30 days prior to randomization, at the 1-month visit, and at the q-4-month study visits thereafter until the end of the study. CD4+ cell counts will be done at the 1-month visit and at the q-4-month study visits until the end of the study. A subset of patients will also have immunophenotyping of CD4+ and CD8+ cell TCR V-beta clones carried out before and during treatment. Another subset of patients at selected sites will have viral cultures performed for phenotypic drug sensitivity testing.

Initially, specimens for 50 randomly chosen patients in the group originally assigned RTV will be identified for resistance testing. Of this group, specimens for those who have received RTV/IDV for more than 1 month will be analyzed for genotypic resistance to obtain an estimate of the rate of resistance development and to estimate the risk of disease progression associated with resistance to RTV/ZDV. Based on these estimates, determination will be made of the total number of patients and specimens in both treatment groups in order to address the primary objective of comparing genotypic resistance in the two groups.]

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

  • Background AR nucleoside therapy is required, although background AR therapy may also be no background therapy. However, the use of protease inhibitors is not recommended as monotherapy unless there is no other alternative. Therefore, patients who are not on AR treatment may be enrolled at the discretion of the clinician.

Allowed:

  • Saquinavir.

Patients must have:

  • Documented HIV infection.
  • A CD4+ cell count <= 100/mm3 within 3 months prior to the study. [AS PER AMENDMENT 3/11/98: CD4+ cell count <= 200/mm3 any time prior to entry].
  • Parental consent if patient is < 18 years old.

Prior Medication:

Allowed:

  • Saquinavir (SQV).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Stage 2 or greater AIDS dementia complex.
  • [AS PER AMENDMENT 10/2/97: Any acute disease or condition that would, in the physician's judgement, contraindicate starting NFV or RTV.]
  • Known hypersensitivity to RTV or any of its ingredients (for patients assigned to RTV therapy).

Concurrent Medication:

Excluded:

  • Concomitant use of protease inhibitors.
  • Concomitant treatments that cannot be discontinued, and in the physician's judgement, should not be taken with NFV or RTV.

AS PER AMENDMENT 10/2/97:

  • For patients randomized to NFV:
  • Concomitant therapy with terfenadine, astemizole, cisapride, triazolam, midazolam, ergot derivatives, amiodarone, quinidine, or rifampin.

For patients randomized to IDV:

  • Concomitant therapy with terfenadine, astemizole, cisapride, triazolam, midazolam, and rifampin.

Patients with any of the following prior symptoms are excluded:

AS PER AMENDMENT 10/2/97:

  • History of clinically significant hypersensitivity reaction to any component of NFV tablets (for patients assigned to NFV therapy).

Prior Medication:

Excluded:

  • Prior use of protease inhibitors except SQV.

[AS PER AMENDMENT 10/2/97:

  • Prior use of IDV for more than 4 weeks or other protease inhibitors (except SQV) for any prior duration.]
  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: NCT00000859

  Hide Study Locations
Locations
United States, California
Community Consortium / UCSF
San Francisco, California, United States, 94110
Community Consortium of San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Denver CPCRA / Denver Public Hlth
Denver, Colorado, United States, 80204
Denver CPCRA / Denver Pub Hlth / Rocky Mt Cancer Ctr Aurora
Denver, Colorado, United States, 80204
Denver Community Program for Clinical Research on AIDS
Denver, Colorado, United States, 80204
United States, District of Columbia
Washington Reg AIDS Prog / Dept of Infect Dis
Washington, District of Columbia, United States, 20422
Infectious Disease Physicians / Northern Virginia
Washington, District of Columbia, United States, 20422
Timothy A Price
Washington, District of Columbia, United States, 20422
Veterans Administration Med Ctr / Regional AIDS Program
Washington, District of Columbia, United States, 20422
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Illinois
AIDS Research Alliance - Chicago
Chicago, Illinois, United States, 60657
United States, Louisiana
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, United States, 70112
Louisiana Community AIDS Research Program
New Orleans, Louisiana, United States, 70112
United States, Maryland
Baltimore TRIALS
Baltimore, Maryland, United States, 21201
Westat / NICHD
Rockville, Maryland, United States, 20850
United States, Michigan
Comprehensive AIDS Alliance of Detroit
Detroit, Michigan, United States, 48201
Henry Ford Hosp
Detroit, Michigan, United States, 48202
Wayne State Univ / Univ Hlth Ctr
Detroit, Michigan, United States, 48201
United States, New Jersey
Mercer Area Early Intervention Services
Camden, New Jersey, United States, 08103
Southern New Jersey AIDS Clinical Trials
Camden, New Jersey, United States, 08103
Southern New Jersey AIDS Cln Trials / Dept of Med
Camden, New Jersey, United States, 08103
North Jersey Community Research Initiative
Newark, New Jersey, United States, 07103
New Jersey Community Research Initiative
Newark, New Jersey, United States, 07103
United States, New Mexico
Partners in Research - New Mexico
Albuquerque, New Mexico, United States, 87131
Partners Research
Albuquerque, New Mexico, United States, 87131
United States, New York
Harlem AIDS Treatment Group
New York, New York, United States, 10037
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
United States, Oregon
The Research and Education Group
Portland, Oregon, United States, 97210
Portland Veterans Adm Med Ctr / Rsch & Education Grp
Portland, Oregon, United States, 97210
United States, Pennsylvania
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
Saint Joseph's Hosp
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
Richmond AIDS Consortium
Richmond, Virginia, United States, 23298
Canada, British Columbia
Saint Paul's Hosp
Vancouver, British Columbia, Canada
Canada, Nova Scotia
QEII Health Science Centre
Halifax, Nova Scotia, Canada
Canada, Ontario
Saint Joseph's Hosp
London, Ontario, Canada
Ottawa Gen Hosp
Ottawa, Ontario, Canada
Sunnybrook Health Science Centre
Toronto, Ontario, Canada
Toronto Gen Hosp
Toronto, Ontario, Canada
Wellesley Hosp
Toronto, Ontario, Canada
Canada, Quebec
Hotel - Dieu de Montreal
Montreal, Quebec, Canada
Montreal Chest Institute
Montreal, Quebec, Canada
SMBD-Jewish Gen Hosp
Montreal, Quebec, Canada
Centre De Recherche En Infectiologie
Ste-Foy, Quebec, Canada
Canada, Saskatchewan
Royal Univ Hosp
Saskatoon, Saskatchewan, Canada
Sponsors and Collaborators
Investigators
Study Chair: Perez G
Study Chair: MacArthur R
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000859     History of Changes
Other Study ID Numbers: CPCRA 042, 11592
Study First Received: November 2, 1999
Last Updated: September 28, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Resistance
Drug Therapy, Combination
HIV Protease Inhibitors
CD4 Lymphocyte Count
Ritonavir
Indinavir
Disease Progression
RNA, Viral
Genotype
Nelfinavir
Anti-HIV Agents
Viral Load

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

ClinicalTrials.gov processed this record on November 20, 2014