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The Safety and Effectiveness of Zidovudine in the Treatment of Patients With Early AIDS Related Complex
This study has been completed.
First Received: November 2, 1999   Last Updated: July 14, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001011
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Phase III

Study Type: Interventional
Study Design: Treatment, Parallel Assignment
Official Title: The Safety and Efficacy of Zidovudine in the Treatment of Patients With Early AIDS Related Complex

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 538
Detailed 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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001011

  Hide Study Locations
Locations
United States, California
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
Palo Alto Veterans Adm Med Ctr / Stanford Univ
Palo Alto, California, United States, 94304
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Stanford Univ School of Medicine
Stanford, California, United States, 94305
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, District of Columbia
George Washington Univ Med Ctr
Washington, District of Columbia, United States, 20037
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mount Sinai Med Ctr
New York, New York, United States, 10029
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Cornell Univ Med Ctr
New York, New York, United States, 10021
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, United States, 10003
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
Columbus Children's Hosp
Columbus, Ohio, United States, 432052696
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, United States, 452670405
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 19107
Univ of Pittsburgh Med School
Pittsburgh, Pennsylvania, United States
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Study Chair: MA Fischl
Study Chair: DD Richman
  More Information

Additional Information:
Publications:
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.
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. 1992;5(9):890-7.
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.
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. 1993 May;6(5):452-8.
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.
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.
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.
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.
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.
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. 1991;4(12):1199-207.

Study ID Numbers: ACTG 016
Study First Received: November 2, 1999
Last Updated: July 14, 2008
ClinicalTrials.gov Identifier: NCT00001011     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Virus Replication
AIDS-Related Complex
Zidovudine

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 25, 2009