A Comparison of Three Treatments for Advanced HIV Disease in Patients Who Have Received Nucleoside Therapy in the Past

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001029
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  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 2

Study Type: Interventional
Study Design: Primary Purpose: 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
Study Completion Date: May 1993
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001029

  Hide Study Locations
Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033
Stanford CRS
Palo Alto, California, United States, 94115
Ucsd, Avrc Crs
San Diego, California, United States, 92103
Ucsf Aids Crs
San Francisco, California, United States
Santa Clara Valley Med. Ctr.
San Jose, California, United States
San Mateo County AIDS Program
San Mateo, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
Northwestern University CRS
Chicago, Illinois, United States
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202
United States, Iowa
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
Hennepin County Med. Ctr., Div. of Infectious Diseases
Minneapolis, Minnesota, United States, 55415
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St. Louis, Missouri, United States
United States, Nebraska
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States, 68198
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Cornell University A2201
New York, New York, United States, 10021
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 10003
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Case CRS
Cleveland, Ohio, United States, 44106
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Puerto Rico
Puerto Rico-AIDS CRS
San Juan, Puerto Rico, 00936
Tanzania
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
Mbeya, Tanzania
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:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001029     History of Changes
Other Study ID Numbers: ACTG 193, 11168
Study First Received: November 2, 1999
Last Updated: March 30, 2012
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:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Didanosine
Zalcitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 18, 2014