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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
This study has been completed.
First Received: November 2, 1999   Last Updated: August 6, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators: Bristol-Myers Squibb
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000625
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Zalcitabine
Drug: Didanosine
Phase II

Study Type: Interventional
Study Design: Treatment, Double-Blind, Safety Study
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

Resource links provided by NLM:


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

Estimated Enrollment: 2100
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.

  Eligibility

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000625

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
UCSD Med Ctr / Pediatrics / Clinical Sciences
La Jolla, California, United States, 920930672
Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr
Sylmar, California, United States, 91342
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Univ of Washington / Children's Hosp of Los Angeles
Los Angeles, California, United States, 90027
Huntington Memorial Hosp / Children's Hosp of Los Angeles
Pasadena, California, United States, 91105
Children's Hosp of Los Angeles
Los Angeles, California, United States, 90027
UCSD / Children's Hosp Los Angeles
Los Angeles, California, United States, 90027
Summitt Med Ctr / San Francisco Gen Hosp
Oakland, California, United States, 94609
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
Olive View Med Ctr
Sylmar, California, United States, 91342
United States, Colorado
Univ Hosp / Univ of Colorado Health Sci Ctr
Denver, Colorado, United States, 80262
Mountain States Reg Hemo Ctr / Univ of Colorado
Denver, Colorado, United States, 80262
Mountain States Hemo Ctr / Univ of Utah
Denver, Colorado, United States, 80262
Saint Joseph's Hosp & Med Ctr / Mtn States Reg Hemo Ctr
Denver, Colorado, United States, 80262
United States, Connecticut
Connecticut Children's Med Ctr
Farmington, Connecticut, United States, 060303805
Yale Univ / New Haven
New Haven, Connecticut, United States, 065102483
United States, District of Columbia
George Washington Univ Med Ctr
Washington, District of Columbia, United States, 20037
Howard Univ
Washington, District of Columbia, United States, 20059
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
HIV Ctr - District of Columbia Gen Hosp
Washington, District of Columbia, United States, 200072197
George Washington Univ / Hershey 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, Georgia
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
Atlanta, Georgia, United States, 303652225
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
Chicago, Illinois, United States, 60611
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Indiana Univ / Riley Hosp for Children
Indianapolis, Indiana, United States, 46202
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
United States, Iowa
Great Plains - Hemophilia / Univ of Iowa Hosp & Clinic
Iowa City, Iowa, United States, 52242
Univ of Iowa Hosp and Clinic
Iowa City, Iowa, United States, 52242
United States, Kentucky
Univ of Louisville / East Tennesee Comprehensive Hem Ctr
Louisville, Kentucky, United States, 40202
United States, Louisiana
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
Tulane Med Ctr Hosp
New Orleans, Louisiana, United States, 70112
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Children's Hosp of Boston
Boston, Massachusetts, United States, 021155724
Boston City Hosp / Pediatrics
Boston, Massachusetts, United States, 02118
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
Worcester, Massachusetts, United States, 01605
Rhode Island Hemophilia Ctr / Med Ctr of Cntrl MA
Worcester, Massachusetts, United States, 01605
Brigham and Women's Hosp
Boston, Massachusetts, United States, 02115
United States, Michigan
Children's Hosp of Michigan
Detroit, Michigan, United States, 48201
Michigan State Univ Hemophilia Comprehensive Care Clinic
Lansing, Michigan, United States, 48912
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
St Paul Ramsey Med Ctr
St Paul, Minnesota, United States, 55101
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, Nebraska
Nebraska Regional Hemophilia Ctr / Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
St Louis Univ Med Ctr / Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New Hampshire
Dartmouth - Hitchcock Med Ctr / Med Ctr Cntrl Massachusetts
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
Robert Wood Johnson Med School / Hershey Med Ctr
New Brunswick, New Jersey, United States, 08903
UMDNJ - New Jersey Med School
Newark, New Jersey, United States, 07107
United States, New York
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Nassau County Med Ctr
East Meadow, New York, United States, 11554
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
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
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
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
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
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Mount Sinai Med Ctr / Hemophilia Treatment Ctr
New York, New York, United States, 10029
Beth Israel Med Ctr
New York, New York, United States, 10003
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
Puerto Genetic Disease Clinic
New York, New York, United States, 10029
Montefiore Med Ctr Adolescent AIDS Program
Bronx, New York, United States, 10467
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
North Shore Univ Hosp
Manhasset, New York, United States, 11030
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
United States, North Carolina
Wake Med Ctr / Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Carolinas Med Ctr
Charlotte, North Carolina, United States, 28203
Wake County Dept of Health
Raleigh, North Carolina, United States, 27610
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Glaxo Wellcome Inc
Research Triangle Park, North Carolina, United States, 27709
United States, Ohio
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
Med College of Ohio
Toledo, Ohio, United States, 43699
Northwest Ohio Hemo Treatment Ctr / Great Lakes Hemo Fdn
Toledo, Ohio, United States, 43606
United States, Oregon
Oregon Health Sciences Univ / Children's Hosp of Los Angeles
Portland, Oregon, United States, 97201
United States, Pennsylvania
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
Hemophilia Ctr of Western PA / Univ of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15219
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Univ of Pittsburgh Med School / Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Med Univ of South Carolina / UNC
Charleston, South Carolina, United States, 29425
United States, Tennessee
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
Knoxville, Tennessee, United States, 37920
United States, Texas
Univ Texas Health Science Ctr / Univ Texas Med School
Houston, Texas, United States, 77030
Univ of Texas Southwestern Med Ctr of Dallas
Dallas, Texas, United States, 75235
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
United States, Wisconsin
Great Lakes Hemophilia Foundation
Wauwatosa, Wisconsin, United States, 532130127
Northern Wisconsin Hemophilia Ctr / Saint Vincent's Hosp
Green Bay, Wisconsin, United States, 54301
Comp Hemo Ctr of Ctrl & N Illinois / Great Lakes Hemo Fdn
Wauwatosa, Wisconsin, United States, 532130127
Youngstown Hemophilia Ctr / Great Lakes Hemophilia Fdn
Wauwatosa, Wisconsin, United States, 53213
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: Katzenstein D
Study Chair: Hammer S
  More Information

Additional Information:
Publications:
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. Review.
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.
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.
[No authors listed] 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.
Katzenstein DA, Hughes MD, Albrecht M, Liou SH, Murphy R, Balfour H, Para M, Hammer S. 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.
Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90.
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.
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.
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.
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.
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.

Study ID Numbers: ACTG 175
Study First Received: November 2, 1999
Last Updated: August 6, 2008
ClinicalTrials.gov Identifier: NCT00000625     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Didanosine
Drug Therapy, Combination
AIDS-Related Complex
Antiviral Agents
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
Zalcitabine
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 27, 2009