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A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Zidovudine
Zalcitabine
Didanosine
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 Zalcitabine, Didanosine, Drug Therapy, Combination, AIDS-Related Complex, Antiviral Agents, Zidovudine

Eligibility Criteria

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

Inclusion Criteria Concurrent Medication: Allowed: PCP prophylaxis, M. tuberculosis prophylaxis, short courses of acyclovir, chronic suppressive acyclovir, pneumovax or Hib vaccine, antibiotics, rEPO and G-CSF for grade 3 or worse anemia and neutropenia, systemic corticosteroids for < 21 days, regularly prescribed medications, and vitamins or herbal therapies. Patients must have: HIV infection without AIDS with CD4 200-500 cells/mm3. PER AMENDMENT 4/5/95: Patients must have remained on ACTG 175 study treatment through 4/30/95 and meet toxicity management criteria for continuing treatment. Subjects taking ACTG 175 crossover treatment are eligible. Exclusion Criteria Co-existing Condition: Patients with the following conditions are excluded: Current AIDS-related condition other than minimal KS, grade 2 or worse peripheral neuropathy, and malignancy requiring systemic therapy. Concurrent Medication: Excluded: Other anti-HIV drugs, biologic response modifiers other than rEPO and G-CSF, systemic cytotoxic chemotherapy, chronic systemic corticosteroids, or any drug that affects AZT glucuronidation or clearance. Concurrent Treatment: Excluded: Radiotherapy other than limited local therapy to skin. Patients with the following prior conditions are excluded: AIDS-related condition other than minimal KS; intolerance to AZT, ddI, or ddC at study doses; and acute or chronic pancreatitis. Prior Medication: Excluded: Acute therapy for an infection or other medical illness within the past 14 days. Current alcohol abuse.

Sites / Locations

  • Alabama Therapeutics CRS
  • USC CRS
  • UCLA CARE Center CRS
  • Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
  • Stanford CRS
  • UCSD Maternal, Child, and Adolescent HIV CRS
  • Ucsd, Avrc Crs
  • Ucsf Aids Crs
  • Santa Clara Valley Med. Ctr.
  • San Mateo County AIDS Program
  • Harbor-UCLA Med. Ctr. CRS
  • University of Colorado Hospital CRS
  • Howard University Hosp., Div. of Infectious Diseases, ACTU
  • Univ. of Miami AIDS CRS
  • Emory Univ. Hemophilia Program Office
  • Univ. of Hawaii at Manoa, Leahi Hosp.
  • Northwestern University CRS
  • Cook County Hosp. CORE Ctr.
  • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Methodist Hosp. of Indiana
  • Univ. of Iowa Healthcare, Div. of Infectious Diseases
  • Tulane Hemophilia Treatment Ctr.
  • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
  • Tulane/LSU Maternal/Child CRS
  • Johns Hopkins Adult AIDS CRS
  • Massachusetts General Hospital ACTG CRS
  • Brigham and Women's Hosp., Div. of Infectious Disease
  • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
  • Bmc Actg Crs
  • Beth Israel Deaconess - East Campus A0102 CRS
  • Beth Israel Deaconess Med. Ctr., ACTG CRS
  • Hennepin County Med. Ctr., Div. of Infectious Diseases
  • University of Minnesota, ACTU
  • St. Louis ConnectCare, Infectious Diseases Clinic
  • Washington U CRS
  • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
  • NJ Med. School CRS
  • SUNY - Buffalo, Erie County Medical Ctr.
  • Beth Israel Med. Ctr. (Mt. Sinai)
  • NY Univ. HIV/AIDS CRS
  • Cornell University A2201
  • Memorial Sloan-Kettering Cancer Ctr.
  • NYU Med. Ctr., Dept. of Medicine
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • Carolinas HealthCare System, Carolinas Med. Ctr.
  • Duke Univ. Med. Ctr. Adult CRS
  • Regional Center for Infectious Disease, Wendover Medical Center CRS
  • Wake County Health and Human Services CRS
  • Univ. of Cincinnati CRS
  • Case CRS
  • MetroHealth CRS
  • The Ohio State Univ. AIDS CRS
  • Hosp. of the Univ. of Pennsylvania CRS
  • University of Washington AIDS CRS
  • Puerto Rico-AIDS CRS
  • Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00000625
Brief Title
A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3
Official Title
A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3
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
November 1995 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.
Detailed Description
Patients are randomized to receive AZT alone, AZT and ddI, AZT and ddC, or ddI alone for at least 2 years. Patients who develop AIDS or whose CD4 count falls to 50 percent or less of baseline are crossed over to another treatment arm. PER AMENDMENT 4/5/95: Study treatment will be available until 10/31/95 at the latest for patients still taking study medications on 4/30/95, so that follow-up trials may be completed and approved.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Zalcitabine, Didanosine, Drug Therapy, Combination, AIDS-Related Complex, Antiviral Agents, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
Double
Enrollment
2100 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Zalcitabine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: PCP prophylaxis, M. tuberculosis prophylaxis, short courses of acyclovir, chronic suppressive acyclovir, pneumovax or Hib vaccine, antibiotics, rEPO and G-CSF for grade 3 or worse anemia and neutropenia, systemic corticosteroids for < 21 days, regularly prescribed medications, and vitamins or herbal therapies. Patients must have: HIV infection without AIDS with CD4 200-500 cells/mm3. PER AMENDMENT 4/5/95: Patients must have remained on ACTG 175 study treatment through 4/30/95 and meet toxicity management criteria for continuing treatment. Subjects taking ACTG 175 crossover treatment are eligible. Exclusion Criteria Co-existing Condition: Patients with the following conditions are excluded: Current AIDS-related condition other than minimal KS, grade 2 or worse peripheral neuropathy, and malignancy requiring systemic therapy. Concurrent Medication: Excluded: Other anti-HIV drugs, biologic response modifiers other than rEPO and G-CSF, systemic cytotoxic chemotherapy, chronic systemic corticosteroids, or any drug that affects AZT glucuronidation or clearance. Concurrent Treatment: Excluded: Radiotherapy other than limited local therapy to skin. Patients with the following prior conditions are excluded: AIDS-related condition other than minimal KS; intolerance to AZT, ddI, or ddC at study doses; and acute or chronic pancreatitis. Prior Medication: Excluded: Acute therapy for an infection or other medical illness within the past 14 days. Current alcohol abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katzenstein D
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hammer S
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
USC CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Stanford CRS
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
UCSD Maternal, Child, and Adolescent HIV CRS
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Ucsd, Avrc Crs
City
San Diego
State/Province
California
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
Country
United States
Facility Name
Santa Clara Valley Med. Ctr.
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
Facility Name
San Mateo County AIDS Program
City
San Mateo
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Harbor-UCLA Med. Ctr. CRS
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Howard University Hosp., Div. of Infectious Diseases, ACTU
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20059
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Emory Univ. Hemophilia Program Office
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30365
Country
United States
Facility Name
Univ. of Hawaii at Manoa, Leahi Hosp.
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp. CORE Ctr.
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Methodist Hosp. of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Univ. of Iowa Healthcare, Div. of Infectious Diseases
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Tulane Hemophilia Treatment Ctr.
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane/LSU Maternal/Child CRS
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hosp., Div. of Infectious Disease
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Bmc Actg Crs
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Beth Israel Deaconess Med. Ctr., ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hennepin County Med. Ctr., Div. of Infectious Diseases
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Minnesota, ACTU
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
St. Louis ConnectCare, Infectious Diseases Clinic
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63112
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
NJ Med. School CRS
City
Newark
State/Province
New Jersey
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Beth Israel Med. Ctr. (Mt. Sinai)
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell University A2201
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
NYU Med. Ctr., Dept. of Medicine
City
New York
State/Province
New York
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Carolinas HealthCare System, Carolinas Med. Ctr.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Regional Center for Infectious Disease, Wendover Medical Center CRS
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
Wake County Health and Human Services CRS
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27610
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MetroHealth CRS
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Puerto Rico-AIDS CRS
City
San Juan
Country
Puerto Rico
Facility Name
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
City
Mbeya
Country
Tanzania

12. IPD Sharing Statement

Citations:
PubMed Identifier
8624066
Citation
Havlir DV, Richman DD. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med. 1996 Jun 1;124(11):984-94. doi: 10.7326/0003-4819-124-11-199606010-00006.
Results Reference
background
PubMed Identifier
8813038
Citation
Hammer SM, Katzenstein DA, Hughes MD, Gundacker H, Schooley RT, Haubrich RH, Henry WK, Lederman MM, Phair JP, Niu M, Hirsch MS, Merigan TC. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. N Engl J Med. 1996 Oct 10;335(15):1081-90. doi: 10.1056/NEJM199610103351501.
Results Reference
background
PubMed Identifier
9875580
Citation
Simpson DM, Katzenstein DA, Hughes MD, Hammer SM, Williamson DL, Jiang Q, Pi JT. Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team. AIDS. 1998 Dec 24;12(18):2425-32. doi: 10.1097/00002030-199818000-00011.
Results Reference
background
PubMed Identifier
10376616
Citation
Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group. Lancet. 1999 Jun 12;353(9169):2014-25.
Results Reference
background
PubMed Identifier
11177402
Citation
Katzenstein DA, Hughes MD, Albrecht M, Liou SH, Murphy R, Balfour H, Para M, Hammer S; ACTG 302 Study Team. Virologic and CD4 cell response to zidovudine or zidovudine and lamivudine following didanosine treatment of human immunodeficiency virus infection. AIDS Res Hum Retroviruses. 2001 Feb 10;17(3):203-10. doi: 10.1089/088922201750063115.
Results Reference
background
PubMed Identifier
11750213
Citation
Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW; Adult AIDS Clinical Trials Unit Outcomes Committee. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90. doi: 10.1016/s0895-4356(01)00449-8.
Results Reference
background
PubMed Identifier
8813039
Citation
Katzenstein DA, Hammer SM, Hughes MD, Gundacker H, Jackson JB, Fiscus S, Rasheed S, Elbeik T, Reichman R, Japour A, Merigan TC, Hirsch MS. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med. 1996 Oct 10;335(15):1091-8. doi: 10.1056/NEJM199610103351502. Erratum In: N Engl J Med 1997 Oct 9;337(15):1097.
Results Reference
background
PubMed Identifier
9498441
Citation
Fiscus SA, Hughes MD, Lathey JL, Pi T, Jackson B, Rasheed S, Elbeik T, Reichman R, Japour A, Byington R, Scott W, Griffith BP, Katzenstein DA, Hammer SM. Changes in virologic markers as predictors of CD4 cell decline and progression of disease in human immunodeficiency virus type 1-infected adults treated with nucleosides. AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998 Mar;177(3):625-33. doi: 10.1086/514248.
Results Reference
background
PubMed Identifier
11015147
Citation
Currier JS, Spino C, Grimes J, Wofsy CB, Katzenstein DA, Hughes MD, Hammer SM, Cotton DJ. Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175 Team. J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):316-24. doi: 10.1097/00126334-200008010-00003.
Results Reference
background
PubMed Identifier
9863872
Citation
Kastrissios H, Suarez JR, Katzenstein D, Girard P, Sheiner LB, Blaschke TF. Characterizing patterns of drug-taking behavior with a multiple drug regimen in an AIDS clinical trial. AIDS. 1998 Dec 3;12(17):2295-303. doi: 10.1097/00002030-199817000-00011.
Results Reference
background
PubMed Identifier
9498440
Citation
Lathey JL, Hughes MD, Fiscus SA, Pi T, Jackson JB, Rasheed S, Elbeik T, Reichman R, Japour A, D'Aquila RT, Scott W, Griffith BP, Hammer SM, Katzenstein DA. Variability and prognostic values of virologic and CD4 cell measures in human immunodeficiency virus type 1-infected patients with 200-500 CD4 cells/mm(3) (ACTG 175). AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998 Mar;177(3):617-24. doi: 10.1086/514250.
Results Reference
background

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A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

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