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

NCT ID: NCT00000841

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1750 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1997-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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. \[AS PER 02/25/97 AMENDMENT: Accrual has been halted because interim analysis has shown triple therapy superior to double-agent therapy. An open label extension phase has been added for the period through 06/30/97. Patients who had been randomized to AZT/3TC are given the option of continuing on assigned ACTG 320 study drugs, crossing over to open-label indinavir, or permanently discontinuing all study therapies and going off study. Patients who were randomized to AZT/3TC plus indinavir or who were crossed to such therapy are given the option of continuing their currently assigned therapies. It is strongly suggested that patients who were on AZT/3TC who wish to receive open-label indinavir consider changing the nucleoside analog component of their regimen if at all possible.\] \[ AS PER 06/06/97 AMENDMENT: The availability of the current ACTG 320 treatment has been further extended for approximately 12 additional weeks (but not beyond 09/30/97). This extension will allow patients to continue receiving study medications until ACTG 372 is open to accrual (the rollover protocol for subjects originally randomized to the triple drug component of ACTG 320 or who are crossed over due to a confirmed study endpoint is finalized).\] \[ AS PER 09/15/97 AMENDMENT: Open-label therapy will be provided for no more than 90 days beyond the enrollment of the first subject on ACTG 372.\]

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Drug Therapy, Combination Acquired Immunodeficiency Syndrome Antiviral Agents Zidovudine Stavudine HIV Protease Inhibitors Lamivudine Indinavir

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Primary Study Purpose

TREATMENT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Indinavir sulfate

Intervention Type DRUG

Lamivudine

Intervention Type DRUG

Stavudine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Hammer SM

Role: STUDY_CHAIR

Squires KE

Role: STUDY_CHAIR

Fischl MA

Role: STUDY_CHAIR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Univ of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Children's Hosp of Los Angeles

Los Angeles, California, United States

Site Status

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, United States

Site Status

UCLA CARE Ctr

Los Angeles, California, United States

Site Status

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Site Status

San Francisco AIDS Clinic / San Francisco Gen Hosp

San Francisco, California, United States

Site Status

San Francisco Gen Hosp

San Francisco, California, United States

Site Status

Stanford at Kaiser / Kaiser Permanente Med Ctr

San Francisco, California, United States

Site Status

San Mateo AIDS Program / Stanford Univ

Stanford, California, United States

Site Status

Stanford Univ Med Ctr

Stanford, California, United States

Site Status

Harbor UCLA Med Ctr

Torrance, California, United States

Site Status

Kaiser Permanente Franklin Med Ctr

Denver, Colorado, United States

Site Status

Mountain States Reg Hemo Ctr / Univ of Colorado

Denver, Colorado, United States

Site Status

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Site Status

George Washington Univ / Hershey Med Ctr

Washington D.C., District of Columbia, United States

Site Status

Georgetown Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

Howard Univ

Washington D.C., District of Columbia, United States

Site Status

Univ of Miami School of Medicine

Miami, Florida, United States

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Emory Univ

Atlanta, Georgia, United States

Site Status

Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr

Atlanta, Georgia, United States

Site Status

Queens Med Ctr

Honolulu, Hawaii, United States

Site Status

Univ of Hawaii

Honolulu, Hawaii, United States

Site Status

Northwestern Univ Med School

Chicago, Illinois, United States

Site Status

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Louis A Weiss Memorial Hosp

Chicago, Illinois, United States

Site Status

Illinois Masonic Med Ctr

Chicago, Illinois, United States

Site Status

Indiana Univ Hosp

Indianapolis, Indiana, United States

Site Status

Division of Inf Diseases/ Indiana Univ Hosp

Indianapolis, Indiana, United States

Site Status

Methodist Hosp of Indiana / Life Care Clinic

Indianapolis, Indiana, United States

Site Status

Univ of Iowa Hosp and Clinic

Iowa City, Iowa, United States

Site Status

Charity Hosp / Tulane Univ Med School

New Orleans, Louisiana, United States

Site Status

Tulane Med Ctr Hosp

New Orleans, Louisiana, United States

Site Status

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Site Status

State of MD Div of Corrections / Johns Hopkins Univ Hosp

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp

Baltimore, Maryland, United States

Site Status

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, United States

Site Status

Boston Med Ctr

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - West Campus

Boston, Massachusetts, United States

Site Status

Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial

Worcester, Massachusetts, United States

Site Status

Hennepin County Med Clinic

Minneapolis, Minnesota, United States

Site Status

Univ of Minnesota

Minneapolis, Minnesota, United States

Site Status

St Paul Ramsey Med Ctr

Saint Paul, Minnesota, United States

Site Status

St Louis Regional Hosp / St Louis Regional Med Ctr

St Louis, Missouri, United States

Site Status

Univ of Nebraska Med Ctr

Omaha, Nebraska, United States

Site Status

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, United States

Site Status

North Shore Univ Hosp

Great Neck, New York, United States

Site Status

Beth Israel Med Ctr

New York, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Kaplan Cancer Ctr / New York Univ Med Ctr

New York, New York, United States

Site Status

Manhattan Veterans Administration / New York Univ Med Ctr

New York, New York, United States

Site Status

Saint Clare's Hosp and Health Ctr

New York, New York, United States

Site Status

Cornell Univ Med Ctr

New York, New York, United States

Site Status

Mem Sloan - Kettering Cancer Ctr

New York, New York, United States

Site Status

St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr / Hemophilia Treatment Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr / Pediatrics

New York, New York, United States

Site Status

Mount Sinai Med Ctr

New York, New York, United States

Site Status

Harlem Hosp Ctr

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY / State Univ of New York

Syracuse, New York, United States

Site Status

Montefiore Med Ctr Adolescent AIDS Program

The Bronx, New York, United States

Site Status

Bronx Veterans Administration / Mount Sinai Hosp

The Bronx, New York, United States

Site Status

Univ of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Carolinas Med Ctr

Charlotte, North Carolina, United States

Site Status

Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Moses H Cone Memorial Hosp

Greensboro, North Carolina, United States

Site Status

Central Prison/Women's Prison in Raleigh / NC

Raleigh, North Carolina, United States

Site Status

Univ of Cincinnati

Cincinnati, Ohio, United States

Site Status

Univ of Kentucky Lexington

Cincinnati, Ohio, United States

Site Status

Case Western Reserve Univ

Cleveland, Ohio, United States

Site Status

Columbus Children's Hosp

Columbus, Ohio, United States

Site Status

Ohio State Univ Hosp Clinic

Columbus, Ohio, United States

Site Status

Milton S Hershey Med Ctr

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson Univ Hosp

Philadelphia, Pennsylvania, United States

Site Status

Med Univ of South Carolina

Charleston, South Carolina, United States

Site Status

Julio Arroyo

West Columbia, South Carolina, United States

Site Status

Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

Knoxville, Tennessee, United States

Site Status

Meharry Med College

Nashville, Tennessee, United States

Site Status

Vanderbilt Univ Med Ctr

Nashville, Tennessee, United States

Site Status

Univ of Texas Galveston

Galveston, Texas, United States

Site Status

Univ Texas Health Science Ctr / Univ Texas Med School

Houston, Texas, United States

Site Status

Univ of Washington

Seattle, Washington, United States

Site Status

Great Lakes Hemophilia Foundation

Wauwatosa, Wisconsin, United States

Site Status

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, , Puerto Rico

Site Status

Univ of Puerto Rico

San Juan, , Puerto Rico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Puerto Rico

References

Explore related publications, articles, or registry entries linked to this study.

Reiter G, Wojnarowski C. Low rate of nelfinavir discontinuation in a clinic population. Int Conf AIDS. 1998;12:1049 (abstract no 60273)

Reference Type BACKGROUND

ACTG 320 trial halted as three-drug arm proves superior. AIDS Patient Care STDS. 1997 Jun;11(3):194. No abstract available.

Reference Type BACKGROUND
PMID: 11361796 (View on PubMed)

Conference updates show promising drug data. AIDS Alert. 1997 Nov;12(11):125-6.

Reference Type BACKGROUND
PMID: 11364769 (View on PubMed)

Baker R. 3-drug therapy reduces deaths and new AIDS-related illnesses by 50%. BETA. 1997 Mar:3-4.

Reference Type BACKGROUND
PMID: 11364527 (View on PubMed)

Demeter LM, Hughes MD, Coombs RW, Jackson JB, Grimes JM, Bosch RJ, Fiscus SA, Spector SA, Squires KE, Fischl MA, Hammer SM. Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med. 2001 Dec 4;135(11):954-64. doi: 10.7326/0003-4819-135-11-200112040-00007.

Reference Type BACKGROUND
PMID: 11730396 (View on PubMed)

Demeter LM, Bosch RJ, Coombs RW, Fiscus S, Bremer J, Johnson VA, Erice A, Jackson JB, Spector SA, Squires KM, Fischl MA, Hughes MD, Hammer SM. Detection of replication-competent human immunodeficiency virus type 1 (HIV-1) in cultures from patients with levels of HIV-1 RNA in plasma suppressed to less than 500 or 50 copies per milliliter. J Clin Microbiol. 2002 Jun;40(6):2089-94. doi: 10.1128/JCM.40.6.2089-2094.2002.

Reference Type BACKGROUND
PMID: 12037070 (View on PubMed)

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)

Reference Type BACKGROUND

Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ Jr, Feinberg JE, Balfour HH Jr, Deyton LR, Chodakewitz JA, Fischl MA. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997 Sep 11;337(11):725-33. doi: 10.1056/NEJM199709113371101.

Reference Type BACKGROUND
PMID: 9287227 (View on PubMed)

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)

Reference Type BACKGROUND

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)

Reference Type BACKGROUND

Levine, AM. HPV Infection and Cervical/Anal Precursor Lesions in the HAART Era. http://www.medscape.com/viewarticle/440151

Reference Type BACKGROUND

Coplan PM, Cook JR, Carides GW, Heyse JF, Wu AW, Hammer SM, Nguyen BY, Meibohm AR, DiNubile MJ; AIDS Clinical Trials Group 320 Study Team. Impact of indinavir on the quality of life in patients with advanced HIV infection treated with zidovudine and lamivudine. Clin Infect Dis. 2004 Aug 1;39(3):426-33. doi: 10.1086/422520. Epub 2004 Jul 19.

Reference Type BACKGROUND
PMID: 15307012 (View on PubMed)

Mrus JM, Williams PL, Tsevat J, Cohn SE, Wu AW. Gender differences in health-related quality of life in patients with HIV/AIDS. Qual Life Res. 2005 Mar;14(2):479-91. doi: 10.1007/s11136-004-4693-z.

Reference Type RESULT
PMID: 15892437 (View on PubMed)

Mrus JM, Schackman BR, Wu AW, Freedberg KA, Tsevat J, Yi MS, Zackin R. Variations in self-rated health among patients with HIV infection. Qual Life Res. 2006 Apr;15(3):503-14. doi: 10.1007/s11136-005-1946-4.

Reference Type RESULT
PMID: 16547789 (View on PubMed)

Cole SR, Stuart EA. Generalizing evidence from randomized clinical trials to target populations: The ACTG 320 trial. Am J Epidemiol. 2010 Jul 1;172(1):107-15. doi: 10.1093/aje/kwq084. Epub 2010 Jun 14.

Reference Type RESULT
PMID: 20547574 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

11294

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 320

Identifier Type: -

Identifier Source: org_study_id