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

NCT ID: NCT00001029

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

654 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1993-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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Zalcitabine Didanosine Drug Therapy, Combination Acquired Immunodeficiency Syndrome Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Zidovudine

Intervention Type DRUG

Zalcitabine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Glaxo Wellcome

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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WK Henry

Role: STUDY_CHAIR

JO Kahn

Role: STUDY_CHAIR

HH Balfour

Role: STUDY_CHAIR

Locations

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USC CRS

Los Angeles, California, United States

Site Status

Stanford CRS

Palo Alto, California, United States

Site Status

Ucsd, Avrc Crs

San Diego, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

Santa Clara Valley Med. Ctr.

San Jose, California, United States

Site Status

San Mateo County AIDS Program

San Mateo, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Site Status

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Methodist Hosp. of Indiana

Indianapolis, Indiana, United States

Site Status

Univ. of Iowa Healthcare, Div. of Infectious Diseases

Iowa City, Iowa, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

Site Status

Hennepin County Med. Ctr., Div. of Infectious Diseases

Minneapolis, Minnesota, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

Omaha, Nebraska, United States

Site Status

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Cornell University A2201

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Puerto Rico-AIDS CRS

San Juan, , Puerto Rico

Site Status

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, , Tanzania

Site Status

Countries

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United States Puerto Rico Tanzania

References

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Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. doi: 10.1086/514571.

Reference Type BACKGROUND
PMID: 9524822 (View on PubMed)

Henry K, Tierney C, Kahn J, Balfour H, Jiang Q, Kmack A, Fischl M. A randomized, double-blind, placebo-controlled study comparing combination nucleoside and triple therapy for the treatment of advanced HIV disease (CD4 less than or equal to 50/mm(3)). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:207 (abstract no LB6)

Reference Type BACKGROUND

Henry K, Erice A, Tierney C, Balfour HH Jr, Fischl MA, Kmack A, Liou SH, Kenton A, Hirsch MS, Phair J, Martinez A, Kahn JO. A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS. AIDS Clinical Trial Group 193A Study Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Dec 1;19(4):339-49. doi: 10.1097/00042560-199812010-00004.

Reference Type BACKGROUND
PMID: 9833742 (View on PubMed)

Other Identifiers

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11168

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 193

Identifier Type: -

Identifier Source: org_study_id