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A Comparison of Three Treatments for Advanced HIV Disease in Patients Who Have Received Nucleoside Therapy in the Past
This study has been completed.
First Received: November 2, 1999   Last Updated: July 29, 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: NCT00001029
  Purpose

To compare the efficacy, safety and tolerance, and other clinical and immunologic effects of zidovudine (AZT) plus zalcitabine (dideoxycytidine; ddC), AZT plus didanosine (ddI), and AZT alternating monthly with ddI as measured by differences in survival among HIV-infected persons who have received 6 or more months of nucleoside monotherapy and have a CD4 count greater than or equal to 50 cells/mm3.

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.


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

Study Type: Interventional
Study Design: Treatment
Official Title: A Randomized, Double-Blind, Three-Arm Study Comparing Combination to Monthly Alternating Nucleoside Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3) With a Prior History of Nucleoside Therapy

Resource links provided by NLM:


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

Estimated Enrollment: 654
Detailed Description:

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

Patients are randomized to one of three treatment arms: AZT plus ddI, AZT plus ddC, and AZT alone alternating monthly with ddI. Half of the patients receiving AZT alternating monthly with ddI will start with AZT, while the other half will start with ddI. Treatment continues until death or termination of the study. Patients are followed every 4 weeks. The study will include a subset of patients for whom virologic, pharmacokinetic, and macroneurologic assessments will be made.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis.

Allowed:

  • Erythropoietin.
  • Prophylaxis for MAI or fungal infections.
  • Antibiotics.
  • Over-the-counter, alternative, or regularly prescribed drugs.
  • Steroids, if for < 21 days.

Concurrent Treatment:

Allowed:

  • Radiation therapy for cutaneous Kaposi's sarcoma.

Patients must have:

  • HIV infection.
  • CD4 count <= 50 cells/mm3.
  • Prior nucleoside monotherapy for at least 6 months.
  • Life expectancy of at least 6 months.

Prior Medication: Required:

  • Nucleoside monotherapy for at least 6 months. Active alcohol or drug abuse.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Severe peripheral neuropathy.
  • Psychological or emotional problems sufficient to prevent study compliance.

Concurrent Medication:

Excluded:

  • Systemic chemotherapy for malignancy.
  • Acute or induction therapy for opportunistic infection.

Patients with the following prior conditions are excluded:

  • History of acute or chronic pancreatitis.
  • Grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.

Prior Medication:

Excluded:

  • Non-study nucleosides or biologic response modifiers within 7 days prior to study entry.
  • Acute therapy for opportunistic process within 14 days prior to study entry.
  • Acute systemic therapy for other medical conditions within 14 days prior to study entry.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001029

  Hide Study Locations
Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
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
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
San Francisco Gen Hosp
San Francisco, California, United States, 94110
Olive View Med Ctr
Sylmar, California, United States, 91342
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Connecticut
Yale Univ / New Haven
New Haven, Connecticut, United States, 065102483
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
Whitman - Walker Clinic / Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 200072197
HIV Ctr - District of Columbia Gen Hosp
Washington, District of Columbia, United States, 200072197
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
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
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Boston Med Ctr
Boston, Massachusetts, United States, 02118
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
Hennepin County Med Clinic
Minneapolis, Minnesota, United States, 55415
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
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
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
North Shore Univ Hosp
Manhasset, New York, United States, 11030
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
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
Montefiore Med Ctr Adolescent AIDS Program
Bronx, New York, United States, 10467
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Comprehensive Health Care Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Med College of Ohio
Toledo, Ohio, United States, 43699
Columbus Children's Hosp
Columbus, Ohio, United States, 432052696
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: WK Henry
Study Chair: JO Kahn
Study Chair: HH Balfour
  More Information

Additional Information:
Publications:
Study ID Numbers: ACTG 193
Study First Received: November 2, 1999
Last Updated: July 29, 2008
ClinicalTrials.gov Identifier: NCT00001029     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
Acquired Immunodeficiency Syndrome
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