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

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Children's Hosp of Los Angeles
Los Angeles, California, United States, 90027
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, Colorado
Mountain States Reg Hemo Ctr / Univ of Colorado
Denver, Colorado, United States, 80262
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
Kaiser Permanente Franklin Med Ctr
Denver, Colorado, United States, 80262
United States, District of Columbia
Howard Univ
Washington, District of Columbia, United States, 20059
George Washington Univ / Hershey Med Ctr
Washington, District of Columbia, United States, 20037
Georgetown Univ Hosp
Washington, District of Columbia, United States, 20037
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
Univ of Miami (Pediatric)
Miami, Florida, United States, 33161
United States, Georgia
Emory Univ
Atlanta, Georgia, United States, 30308
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
Atlanta, Georgia, United States, 303652225
United States, Hawaii
Queens Med Ctr
Honolulu, Hawaii, United States, 96816
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Illinois Masonic Med Ctr
Chicago, Illinois, United States, 606575147
Louis A Weiss Memorial Hosp
Chicago, Illinois, United States, 60640
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
Division of Inf Diseases/ Indiana Univ Hosp
Indianapolis, Indiana, United States, 46202
United States, Iowa
Univ of Iowa Hosp and Clinic
Iowa City, Iowa, United States, 52242
United States, Louisiana
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
Tulane Med Ctr Hosp
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
Worcester, Massachusetts, United States, 01605
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
Hennepin County Med Clinic
Minneapolis, Minnesota, United States, 55415
St Paul Ramsey Med Ctr
St Paul, Minnesota, United States, 55101
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New York
Montefiore Med Ctr Adolescent AIDS Program
Bronx, New York, United States, 10467
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
North Shore Univ Hosp
Great Neck, New York, United States, 11021
Mount Sinai Med Ctr / Pediatrics
New York, New York, United States, 10029
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Harlem Hosp Ctr
New York, New York, United States, 10037
Manhattan Veterans Administration / New York Univ Med Ctr
New York, New York, United States, 10016
St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr
New York, New York, United States, 10021
Cornell Univ Med Ctr
New York, New York, United States, 10021
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Mount Sinai Med Ctr
New York, New York, United States, 10029
Mount Sinai Med Ctr / Hemophilia Treatment Ctr
New York, New York, United States, 10029
Beth Israel Med Ctr
New York, New York, United States, 10003
Kaplan Cancer Ctr / New York Univ Med Ctr
New York, New York, United States, 10016
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Carolinas Med Ctr
Charlotte, North Carolina, United States, 28203
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
Central Prison/Women's Prison in Raleigh / NC
Raleigh, North Carolina, United States, 276260540
United States, Ohio
Univ of Kentucky Lexington
Cincinnati, Ohio, United States, 45267
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Columbus Children's Hosp
Columbus, Ohio, United States, 432052696
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
United States, South Carolina
Med Univ of South Carolina
Charleston, South Carolina, United States, 294253312
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Tennessee
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
Knoxville, Tennessee, United States, 37920
Meharry Med College
Nashville, Tennessee, United States, 37203
Vanderbilt Univ Med Ctr
Nashville, Tennessee, United States, 37203
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
Univ Texas Health Science Ctr / Univ Texas Med School
Houston, Texas, United States, 77030
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
United States, Wisconsin
Great Lakes Hemophilia Foundation
Wauwatosa, Wisconsin, United States, 532130127
Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics
Bayamon, Puerto Rico, 00956
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
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 20, 2014