The Safety and Effectiveness of Lamivudine Plus Stavudine or Zidovudine in HIV-Infected Patients Who Have Taken Zidovudine

A Randomized Double-Blind Study of Safety, Virologic and Immunological Effects of Stavudine Plus Lamivudine (3TC) Versus Zidovudine Plus Lamivudine in HIV-Infected Subjects Following At Least Six Months of Zidovudine Therapy

To compare the magnitude and durability of the reduction in plasma HIV RNA in the two treatment groups over the first 12 weeks of treatment. To determine the safety of each of the two treatment groups.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Indinavir sulfate; Drug: Lamivudine; Drug: Stavudine; Drug: Zidovudine

Detailed Description

Patients will be randomized to either Stavudine (d4T) + Lamivudine (3TC) + Zidovudine placebo or Zidovudine (ZDV) + Lamivudine + Stavudine placebo. Patients whose plasma HIV RNA levels remain >= 500 copies/ml after 8 weeks of blinded double combination therapy will have indinavir added to their treatment regimen at the week 12 visit.

• Study Type: Interventional
• Enrollment: 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • North York, Ontario, Canada
      • Sunnybrook Health Science Ctr
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal Gen Hosp / Div of Clin Immuno and Allergy
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Univ of Puerto Rico School of Medicine
• United States
  • California
    • Torrance, California, United States, 90502
      • Harbor UCLA Med Ctr
  • Florida
    • Tampa, Florida, United States, 33612
      • Univ of South Florida
  • New York
    • Stony Brook, New York, United States, 11794
      • SUNY at Stony Brook / Division of Infectious Diseases
  • Texas
    • Houston, Texas, United States, 77006
      • Houston Clinical Research Network / Div of Montrose Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Univ of Utah / School of Medicine / Div of Infect Dis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients must have:

• At least six months of prior cumulative ZDV therapy.
• Qualifying plasma HIV RNA count of >= 4 log10 copies/ml obtained within 2 weeks of randomization.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

• Presence of newly diagnosed AIDS defining opportunistic infection requiring acute therapy at time of enrollment.
• Intractable diarrhea (>= 6 loose stools/day for >= 7 consecutive days).
• Signs and symptoms of bilateral peripheral neuropathy >= grade 2 at the time of screening.
• Inability to tolerate oral medication.
• Any other clinical conditions that in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.

Concurrent Medication:

Excluded:

• Therapy with agents with systemic myelosuppressive, neurotoxic pancreatotoxic, hepatotoxic or cytotoxic potential.
• Therapy with rifampin, rifabutin, terfenadine, astemizole, cisapride, triazolam, midazolam and ketoconazole at any time while on indinavir therapy.

Patients with any of the following prior conditions or symptoms are excluded:

• History of acute or chronic pancreatitis.
• Prior history of bilateral peripheral neuropathy.
• Intractable diarrhea (>= 6 loose stools/day for >= 7 consecutive days) within 30 days prior to study entry.

Prior Medication:

Excluded:

• Any prior antiretroviral therapy except for ddI, ddC, 3TC or ZDV (for ZDV, as specified in inclusion criteria).
• Previous therapy with agents with significant systemic myelosuppressive, neurotoxic pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start.
• Therapy with rifampin, rifabutin, terfenadine, astemizole, cisapride, triazolam, midazolam and ketoconazole within 2 weeks prior to starting indinavir.
• Any other prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing regimen.

Risk Behavior:

Excluded:

• Active alcohol abuse, sufficient in the investigator's opinion, to prevent compliance with study therapy or to increase the risk of developing pancreatitis.

Required:

At least 6 months of prior cumulative ZDV therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: June 1, 1996
• Primary Completion (Actual): December 1, 1997
• Study Completion (Actual): December 1, 1997

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): May 4, 2011
• Last Update Submitted That Met QC Criteria: April 28, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Anti-HIV Agents; HIV-1; Stavudine; Lamivudine; RNA, Viral; Viral Load
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lamivudine; Zidovudine; Stavudine; Indinavir
• Other Study ID Numbers: 244B; AI455-048

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No