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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000841
• Other study ID #: ACTG 320
• Secondary ID: 11294
• Status: Completed
• Phase: Phase 3
• Est. completion date: June 1997

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.]

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1750
• Est. completion date: June 1997
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections

Intervention

Drug:
• Indinavir sulfate

• Lamivudine

• Stavudine

• Zidovudine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia
United States	Emory Univ	Atlanta	Georgia
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	State of MD Div of Corrections / Johns Hopkins Univ Hosp	Baltimore	Maryland
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Boston Med Ctr	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York
United States	Montefiore Med Ctr Adolescent AIDS Program	Bronx	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Carolinas Med Ctr	Charlotte	North Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Illinois Masonic Med Ctr	Chicago	Illinois
United States	Louis A Weiss Memorial Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Univ of Kentucky Lexington	Cincinnati	Ohio
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	Columbus Children's Hosp	Columbus	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Kaiser Permanente Franklin Med Ctr	Denver	Colorado
United States	Mountain States Reg Hemo Ctr / Univ of Colorado	Denver	Colorado
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Texas Galveston	Galveston	Texas
United States	North Shore Univ Hosp	Great Neck	New York
United States	Moses H Cone Memorial Hosp	Greensboro	North Carolina
United States	Milton S Hershey Med Ctr	Hershey	Pennsylvania
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	Univ Texas Health Science Ctr / Univ Texas Med School	Houston	Texas
United States	Division of Inf Diseases/ Indiana Univ Hosp	Indianapolis	Indiana
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana
United States	Univ of Iowa Hosp and Clinic	Iowa City	Iowa
United States	Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr	Knoxville	Tennessee
United States	Children's Hosp of Los Angeles	Los Angeles	California
United States	UCLA CARE Ctr	Los Angeles	California
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Hennepin County Med Clinic	Minneapolis	Minnesota
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Meharry Med College	Nashville	Tennessee
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	Charity Hosp / Tulane Univ Med School	New Orleans	Louisiana
United States	Tulane Med Ctr Hosp	New Orleans	Louisiana
United States	Tulane Univ School of Medicine	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Kaplan Cancer Ctr / New York Univ Med Ctr	New York	New York
United States	Manhattan Veterans Administration / New York Univ Med Ctr	New York	New York
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Mount Sinai Med Ctr / Hemophilia Treatment Ctr	New York	New York
United States	Mount Sinai Med Ctr / Pediatrics	New York	New York
United States	Saint Clare's Hosp and Health Ctr	New York	New York
United States	St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr	New York	New York
United States	Univ of Nebraska Med Ctr	Omaha	Nebraska
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	Central Prison/Women's Prison in Raleigh / NC	Raleigh	North Carolina
United States	Univ of Rochester Medical Center	Rochester	New York
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri
United States	St Paul Ramsey Med Ctr	Saint Paul	Minnesota
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California
United States	San Francisco Gen Hosp	San Francisco	California
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Univ of Washington	Seattle	Washington
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	SUNY / State Univ of New York	Syracuse	New York
United States	Harbor UCLA Med Ctr	Torrance	California
United States	George Washington Univ / Hershey Med Ctr	Washington	District of Columbia
United States	Georgetown Univ Hosp	Washington	District of Columbia
United States	Howard Univ	Washington	District of Columbia
United States	Great Lakes Hemophilia Foundation	Wauwatosa	Wisconsin
United States	Julio Arroyo	West Columbia	South Carolina
United States	Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (15)

ACTG 320 trial halted as three-drug arm proves superior. AIDS Patient Care STDS. 1997 Jun;11(3):194. — View Citation

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

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. — View Citation

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

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)

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. Epub 2004 Jul 19. — View Citation

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. — View Citation

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)

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. — View Citation

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)

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. — View Citation

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

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. — View Citation

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. — View Citation

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

* Note: There are 15 references in all — Click here to view all references