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

  Show 37 Study Locations
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
Zalcitabine
Didanosine
Zidovudine
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 August 01, 2014