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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Virus Replication, AIDS-Related Complex, Zidovudine

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Los Angeles County - USC Med Ctr
  • UCLA CARE Ctr
  • Palo Alto Veterans Adm Med Ctr / Stanford Univ
  • Univ of California / San Diego Treatment Ctr
  • Stanford at Kaiser / Kaiser Permanente Med Ctr
  • Stanford Univ School of Medicine
  • Harbor UCLA Med Ctr
  • George Washington Univ Med Ctr
  • Univ of Miami School of Medicine
  • Northwestern Univ Med School
  • Indiana Univ Hosp
  • Johns Hopkins Hosp
  • Harvard (Massachusetts Gen Hosp)
  • Beth Israel Deaconess - West Campus
  • Univ of Minnesota
  • St Louis Regional Hosp / St Louis Regional Med Ctr
  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
  • Jack Weiler Hosp / Bronx Municipal Hosp
  • Montefiore Med Ctr / Bronx Municipal Hosp
  • Bronx Veterans Administration / Mount Sinai Hosp
  • SUNY / Erie County Med Ctr at Buffalo
  • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
  • Beth Israel Med Ctr / Peter Krueger Clinic
  • Bellevue Hosp / New York Univ Med Ctr
  • Cornell Univ Med Ctr
  • Saint Luke's - Roosevelt Hosp Ctr
  • Mount Sinai Med Ctr
  • Univ of Rochester Medical Center
  • SUNY - Stony Brook
  • SUNY / State Univ of New York
  • Univ of North Carolina
  • Duke Univ Med Ctr
  • Holmes Hosp / Univ of Cincinnati Med Ctr
  • Univ Hosp of Cleveland / Case Western Reserve Univ
  • Columbus Children's Hosp
  • Ohio State Univ Hosp Clinic
  • Thomas Jefferson Univ Hosp
  • Univ of Pittsburgh Med School
  • Julio Arroyo
  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001011
Brief Title
The Safety and Effectiveness of Zidovudine in the Treatment of Patients With Early AIDS Related Complex
Official Title
The Safety and Efficacy of Zidovudine in the Treatment of Patients With Early AIDS Related Complex
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 1995 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Virus Replication, AIDS-Related Complex, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Enrollment
538 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MA Fischl
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
DD Richman
Official's Role
Study Chair
Facility Information:
Facility Name
Los Angeles County - USC Med Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA CARE Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Palo Alto Veterans Adm Med Ctr / Stanford Univ
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Univ of California / San Diego Treatment Ctr
City
San Diego
State/Province
California
ZIP/Postal Code
921036325
Country
United States
Facility Name
Stanford at Kaiser / Kaiser Permanente Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Stanford Univ School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Harbor UCLA Med Ctr
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
George Washington Univ Med Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Univ of Miami School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Northwestern Univ Med School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Johns Hopkins Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Harvard (Massachusetts Gen Hosp)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess - West Campus
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Univ of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St Louis Regional Hosp / St Louis Regional Med Ctr
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63112
Country
United States
Facility Name
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Jack Weiler Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10465
Country
United States
Facility Name
Montefiore Med Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Bronx Veterans Administration / Mount Sinai Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
City
Elmhurst
State/Province
New York
ZIP/Postal Code
11373
Country
United States
Facility Name
Beth Israel Med Ctr / Peter Krueger Clinic
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Saint Luke's - Roosevelt Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Mount Sinai Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY - Stony Brook
City
Stony Brook
State/Province
New York
ZIP/Postal Code
117948153
Country
United States
Facility Name
SUNY / State Univ of New York
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Duke Univ Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Holmes Hosp / Univ of Cincinnati Med Ctr
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Univ Hosp of Cleveland / Case Western Reserve Univ
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Columbus Children's Hosp
City
Columbus
State/Province
Ohio
ZIP/Postal Code
432052696
Country
United States
Facility Name
Ohio State Univ Hosp Clinic
City
Columbus
State/Province
Ohio
ZIP/Postal Code
432101228
Country
United States
Facility Name
Thomas Jefferson Univ Hosp
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Univ of Pittsburgh Med School
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Julio Arroyo
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
1970466
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. doi: 10.7326/0003-4819-112-10-727.
Results Reference
background
PubMed Identifier
1512689
Citation
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.
Results Reference
background
PubMed Identifier
1376654
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. doi: 10.1016/0090-1229(92)90060-2.
Results Reference
background
PubMed Identifier
8483109
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.
Results Reference
background
PubMed Identifier
8528732
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. doi: 10.1097/00042560-199601010-00006.
Results Reference
background
PubMed Identifier
7680058
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. doi: 10.1093/infdis/167.3.526.
Results Reference
background
PubMed Identifier
2168908
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.
Results Reference
background
PubMed Identifier
8101011
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. doi: 10.1002/sim.4780120904.
Results Reference
background
PubMed Identifier
1942422
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.
Results Reference
background
PubMed Identifier
1682473
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.
Results Reference
background

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

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