A Study of Indinavir Sulfate Plus Zidovudine (AZT) Plus Lamivudine in HIV-Infected Patients Who Have Taken AZT for Six or More Months

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000841
First received: November 2, 1999
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

To determine the clinical efficacy of indinavir sulfate or placebo in combination with zidovudine ( AZT ) and lamivudine ( 3TC ) in AIDS patients.

Protease inhibitors such as indinavir sulfate may be effective in patients with advanced HIV disease who have received prior AZT therapy. Since studies suggest that triple drug therapy may have an advantage over both monotherapy and two drug therapy, the combination of indinavir sulfate with AZT and 3TC should be evaluated.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Phase III Study of Indinavir Sulfate With Open-Label Zidovudine (AZT) and Lamivudine (3TC) in Subjects With HIV Infection With CD4 Cell Counts <= 200 Cells/mm3 and >= 6 Months of Prior AZT Experience

Resource links provided by NLM:


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

Estimated Enrollment: 1750
Study Completion Date: June 1997
Detailed Description:

Protease inhibitors such as indinavir sulfate may be effective in patients with advanced HIV disease who have received prior AZT therapy. Since studies suggest that triple drug therapy may have an advantage over both monotherapy and two drug therapy, the combination of indinavir sulfate with AZT and 3TC should be evaluated.

Patients are randomized to receive open-label AZT and 3TC with or without indinavir sulfate for at least 48 weeks. Patients who develop intolerance to AZT or have progressive disease after 24 weeks on study may substitute stavudine ( d4T ) for AZT. Patients are followed at weeks 4, 8, 16, 24, 32, 40, and 48 and every 8 weeks thereafter up to week 96. [AS PER 02/25/97 AMENDMENT: Accrual has been halted because interim analysis has shown triple therapy superior to double-agent therapy. An open label extension phase has been added for the period through 06/30/97. Patients who had been randomized to AZT/3TC are given the option of continuing on assigned ACTG 320 study drugs, crossing over to open-label indinavir, or permanently discontinuing all study therapies and going off study. Patients who were randomized to AZT/3TC plus indinavir or who were crossed to such therapy are given the option of continuing their currently assigned therapies. It is strongly suggested that patients who were on AZT/3TC who wish to receive open-label indinavir consider changing the nucleoside analog component of their regimen if at all possible.] [ AS PER 06/06/97 AMENDMENT: The availability of the current ACTG 320 treatment has been further extended for approximately 12 additional weeks (but not beyond 09/30/97). This extension will allow patients to continue receiving study medications until ACTG 372 is open to accrual (the rollover protocol for subjects originally randomized to the triple drug component of ACTG 320 or who are crossed over due to a confirmed study endpoint is finalized).] [ AS PER 09/15/97 AMENDMENT: Open-label therapy will be provided for no more than 90 days beyond the enrollment of the first subject on ACTG 372.]

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis.

Allowed:

  • Topical or oral antifungal agents (other than oral ketoconazole).
  • Approved agents for opportunistic infections.
  • Antibiotics unless specifically excluded.
  • Systemic corticosteroids for no more than 21 days.
  • Vitamins.
  • Recombinant erythropoietin.
  • G-CSF.
  • Regularly prescribed medications such as allergy medications, antidepressants, antipyretics, analgesics, oral contraceptives, megestrol, and testosterone.

Concurrent Treatment:

Allowed:

  • Acupuncture.
  • Visualization techniques.

Patients must have:

  • HIV infection.
  • CD4 count <= 200 cells/mm3.
  • At least 6 months total prior AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy requiring systemic therapy other than minimal Kaposi's sarcoma.

Concurrent Medication:

Excluded:

  • Antiretrovirals other than study drugs.
  • Rifabutin and rifampin.
  • Investigational drugs other than indinavir sulfate.
  • Systemic cytotoxic chemotherapy.
  • Oral ketoconazole.
  • Chronic systemic corticosteroids.
  • Herbal therapies.

Patients with the following prior conditions are excluded:

  • Unexplained temperature > 38.5 C for any 7 days within 30 days prior to study entry.
  • Chronic diarrhea persisting for 15 days within 30 days prior to study entry.
  • History of acute or chronic pancreatitis.
  • Acute hepatitis within 30 days prior to study entry.
  • Grade 2 or worse bilateral peripheral neuropathy within 60 days prior to study entry.
  • Dose-limiting intolerance to prior AZT at 600 mg/day.

Prior Medication:

Excluded:

  • More than 1 week of prior 3TC.
  • Any prior protease inhibitors.
  • Rifampin or rifabutin within 14 days prior to study entry.

Excluded within 30 days prior to study entry:

  • Erythropoietin.
  • G-CSF or GM-CSF.
  • Non-nucleoside reverse transcriptase inhibitors.
  • Interferons.
  • Interleukins.
  • HIV vaccines.
  • Any experimental therapy.
  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: NCT00000841

  Show 87 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Hammer SM
Study Chair: Squires KE
Study Chair: Fischl MA
  More Information

Additional Information:
Publications:
Reiter G, Wojnarowski C. Low rate of nelfinavir discontinuation in a clinic population. Int Conf AIDS. 1998;12:1049 (abstract no 60273)
Coplan P, Cook J, Carides G, Nguyen BY, Testa M. Impact of indinavir with zidovudine and lamivudine on quality of life for HIV patients with < or = 200 CD4 in ACTG 320. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:86 (abstract no 101)
Demeter LM, Degruttola V, Eshleman S, Jackson JB, Hughes M, Hammer SM. Baseline (BL) HIV-1 protease (PR) and reverse transcriptase (RT) genotype as a predictor of response to ZDV+3TC+indinavir (IDV). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:92 (abstract no 131)
Freedberg KA, Goldie SJ, Paltiel AD, Losina E, Cohen CJ, Seage GR, Craven DE, Zhang H, Kimmel AD, Sullivan LM, Weinstein MC. Combination antiretroviral therapy is both effective and cost-effective. 39th Intersci Conf Antimicrob Agents Chemother. 1999 Sept 26-29 (abstract no I-2070)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000841     History of Changes
Other Study ID Numbers: ACTG 320, 11294
Study First Received: November 2, 1999
Last Updated: July 26, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Antiviral Agents
Zidovudine
Stavudine
HIV Protease Inhibitors
Lamivudine
Indinavir

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

ClinicalTrials.gov processed this record on August 21, 2014