The Safety and Effectiveness of Zidovudine in the Treatment of Patients With Early AIDS Related Complex

HIV Infections Clinical Trial

Official title:

The Safety and Efficacy of Zidovudine in the Treatment of Patients With Early AIDS Related Complex

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001011
• Other study ID #: ACTG 016
• Secondary ID: 10992
• Status: Completed
• Phase: Phase 3
• Est. completion date: February 1995

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 safety and usefulness of zidovudine (AZT) for the treatment of patients with early symptomatic HIV infection or early AIDS related complex (ARC). The ability of AZT to suppress HIV, to improve body defenses, and to prevent the occurrence or development of AIDS or advanced ARC is being evaluated. In one human study, patients with AIDS or advanced ARC who received AZT had fewer life-threatening infections, improved in weight and performance, and lived longer than patients who received a placebo (inactive medication). Further studies are needed because toxic effects associated with the use of AZT were noted and the long-term effectiveness and toxicity of AZT are still unknown. It is also unknown if AZT will benefit patients with less severe HIV infections such as early ARC or PGL.

Description:

In one human study, patients with AIDS or advanced ARC who received AZT had fewer life-threatening infections, improved in weight and performance, and lived longer than patients who received a placebo (inactive medication). Further studies are needed because toxic effects associated with the use of AZT were noted and the long-term effectiveness and toxicity of AZT are still unknown. It is also unknown if AZT will benefit patients with less severe HIV infections such as early ARC or PGL. Patients accepted into the study are randomly assigned to receive either AZT or placebo. Treatment continues for a minimum of 104 weeks beyond the time the last patient enters the study. If the study medication causes toxic effects, the dose is decreased or temporarily stopped, and if the toxic effects are severe, then the medication will be stopped permanently. Participants visit the clinic every 2 weeks during the first 16 weeks and once a month thereafter. Throughout the study frequent blood samples are taken to monitor the effectiveness and safety of the treatment. AMENDED: The placebo arm has been discontinued as of August 3, 1989 and the AZT dose has been reduced.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 538
• Est. completion date: February 1995
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria

• Patients must have a positive antibody to HIV confirmed by a federally licensed ELISA test kit.
• The CD4 cell count must be 201 - 799 cells/mm3 measured on two separate occasions within 60 days at least 72 hours apart prior to study entry (at least 1 of 2 counts and the mean must be < 800 cells/mm3, and at least 1 of 2 counts and the mean must be > 200 cells/mm3). The last count must be within 14 days of study entry. Concurrent Medication:

Allowed:

• Acetaminophen and acetaminophen products but use should be minimized. Continuous use for > 72 hours is discouraged.
• Aerosolized pentamidine. Prior Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia with aerosolized pentamidine of 300 mg every 4 weeks through the Respirgard II nebulizer if patient has CD4(+) count < 200 cells/mm3 measured on 2 determinations at least 48 hours apart. Exclusion Criteria Concurrent Medication:

Excluded:

• Other antiretroviral agents, biologic modifiers or corticosteroids.
• Other experimental medications.
• Systemic chemoprophylaxis of Pneumocystic carinii pneumonia (PCP) - aerosolized pentamidine is allowed. Prior Medication:

Excluded:

• Zidovudine (AZT).
• Other antiretroviral agents.
• Excluded within 30 days of study entry:
• Biologic modifiers or corticosteroids.
• Excluded within 60 days of study entry:
• Ribavirin. Prior Treatment:

Excluded within 30 days of study entry:

• Blood transfusions.

Patients may not have any of the following diseases or symptoms:

• Active oral candidiasis at entry.
• An opportunistic infection or malignancy fulfilling the definition of AIDS (CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome).
• Temperature > 38.5 degrees C persisting for > 14 consecutive days or > 15 days in a 30-day interval present at entry.
• Chronic diarrhea defined as = or > 3 liquid stools per day, persisting for > 14 days without a definable cause during the past 2 years.
• HIV neurologic disease as manifested by motor abnormalities including impaired rapid eye movements or ataxia; motor weakness in the lower extremities; sensory deficit consistent with a peripheral neuropathy; bladder or bowel incontinence.
• Concurrent neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• Subjects with hemophilia should be evaluated and treated under the hemophilia protocols, if available at that ACTG.

Patients may not have any of the following diseases or symptoms:

• Active oral candidiasis at entry.
• An opportunistic infection or malignancy fulfilling the definition of AIDS (CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome).
• Temperature > 38.5 degrees C persisting for > 14 consecutive days or > 15 days in a 30-day interval present at entry.
• Chronic diarrhea defined as = or > 3 liquid stools per day, persisting for > 14 days without a definable cause during the past 2 years.
• HIV neurologic disease as manifested by motor abnormalities including impaired rapid eye movements or ataxia; motor weakness in the lower extremities; sensory deficit consistent with a peripheral neuropathy; bladder or bowel incontinence.
• Concurrent neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• Subjects with hemophilia should be evaluated and treated under the hemophilia protocols, if available at that ACTG. Active drug or alcohol abuse.

Related Conditions & MeSH terms

• AIDS-Related Complex
• HIV Infections

Intervention

Drug:
• Zidovudine

Locations

Country	Name	City	State
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	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	Northwestern Univ Med School	Chicago	Illinois
United States	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio
United States	Univ Hosp of Cleveland / 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	Duke Univ Med Ctr	Durham	North Carolina
United States	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA CARE Ctr	Los Angeles	California
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr / Peter Krueger Clinic	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Saint Luke's - Roosevelt Hosp Ctr	New York	New York
United States	Palo Alto Veterans Adm Med Ctr / Stanford Univ	Palo Alto	California
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh Med School	Pittsburgh	Pennsylvania
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	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Univ of Washington	Seattle	Washington
United States	Stanford Univ School of Medicine	Stanford	California
United States	SUNY - Stony Brook	Stony Brook	New York
United States	SUNY / State Univ of New York	Syracuse	New York
United States	Harbor UCLA Med Ctr	Torrance	California
United States	George Washington Univ Med Ctr	Washington	District of Columbia
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

References & Publications (10)

Bass HZ, Hardy WD, Mitsuyasu RT, Wang YX, Cumberland W, Fahey JL. Eleven lymphoid phenotypic markers in HIV infection: selective changes induced by zidovudine treatment. J Acquir Immune Defic Syndr (1988). 1992;5(9):890-7. — View Citation

Bass HZ, Nishanian P, Hardy WD, Mitsuyasu RT, Esmail E, Cumberland W, Fahey JL. Immune changes in HIV-1 infection: significant correlations and differences in serum markers and lymphoid phenotypic antigens. Clin Immunol Immunopathol. 1992 Jul;64(1):63-70. — View Citation

Fischl MA, Richman DD, Hansen N, Collier AC, Carey JT, Para MF, Hardy WD, Dolin R, Powderly WG, Allan JD, et al. The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group. Ann Intern Med. 1990 May 15;112(10):727-37. — View Citation

Jacobson MA, Gundacker H, Hughes M, Fischl M, Volberding P. Zidovudine side effects as reported by black, Hispanic, and white/non-Hispanic patients with early HIV disease: combined analysis of two multicenter placebo-controlled trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jan 1;11(1):45-52. — View Citation

Kozal MJ, Shafer RW, Winters MA, Katzenstein DA, Merigan TC. A mutation in human immunodeficiency virus reverse transcriptase and decline in CD4 lymphocyte numbers in long-term zidovudine recipients. J Infect Dis. 1993 Mar;167(3):526-32. — View Citation

Lagakos S, Fischl MA, Stein DS, Lim L, Volberding P. Effects of zidovudine therapy in minority and other subpopulations with early HIV infection. JAMA. 1991 Nov 20;266(19):2709-12. — View Citation

Lin DY, Fischl MA, Schoenfeld DA. Evaluating the role of CD4-lymphocyte counts as surrogate endpoints in human immunodeficiency virus clinical trials. Stat Med. 1993 May 15;12(9):835-42. — View Citation

McCorkindale C, Dybevik K, Coulston AM, Sucher KP. Nutritional status of HIV-infected patients during the early disease stages. J Am Diet Assoc. 1990 Sep;90(9):1236-41. — View Citation

Melnick SL, Hannan P, Decher L, Little JW, Rhame FS, Balfour HH Jr, Volberding P. Increasing CD8+ T lymphocytes predict subsequent development of intraoral lesions among individuals in the early stages of infection by the human immunodeficiency virus. J Acquir Immune Defic Syndr (1988). 1991;4(12):1199-207. — View Citation

Wu AW, Rubin HR, Mathews WC, Brysk LM, Bozzette SA, Hardy WD, Atkinson JH, Grant I, Spector SA, McCutchan JA, et al. Functional status and well-being in a placebo-controlled trial of zidovudine in early symptomatic HIV infection. J Acquir Immune Defic Syndr (1988). 1993 May;6(5):452-8. — View Citation