A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To evaluate and compare the effectiveness and toxicity associated with didanosine ( ddI ) and zalcitabine ( dideoxycytidine; ddC ) in patients with HIV infection who are intolerant of or have failed zidovudine ( AZT ) therapy.

Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT.

After baseline screening, patients are randomized to one of two treatment arms (ddI or ddC). Subjects are evaluated biweekly for the first 4 weeks of study, at 2 months, and every other month thereafter. Three dose levels of ddI (based on patient's weight at study entry) are compared with two dose levels of ddC (also based on patient weight). Patients who reach a new progression-of-disease primary endpoint after at least 12 weeks of treatment or a drug intolerance endpoint have the option of switching over to the alternate study drug; however, participants are encouraged to remain on their original drug assignment whenever possible. For any switchover, patients must be off the originally assigned drug for at least 72 hours before switching. Only one switchover is allowed.

Study Type

Interventional

Enrollment

400

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • Community Consortium of San Francisco
    • Colorado
      • Denver, Colorado, United States, 802044507
        • Denver CPCRA / Denver Public Hlth
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Hill Health Corp
    • Delaware
      • Wilmington, Delaware, United States, 19899
        • Wilmington Hosp / Med Ctr of Delaware
    • District of Columbia
      • Washington, District of Columbia, United States, 20422
        • Veterans Administration Med Ctr / Regional AIDS Program
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • AIDS Research Consortium of Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60657
        • AIDS Research Alliance - Chicago
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hosp
      • Detroit, Michigan, United States, 48201
        • Comprehensive AIDS Alliance of Detroit
    • New Jersey
      • Newark, New Jersey, United States, 071032842
        • North Jersey Community Research Initiative
    • New York
      • Bronx, New York, United States, 10456
        • Bronx Lebanon Hosp Ctr
      • New York, New York, United States, 10011
        • Clinical Directors Network of Region II
      • New York, New York, United States, 10037
        • Harlem AIDS Treatment Group / Harlem Hosp Ctr
    • Oregon
      • Portland, Oregon, United States, 972109951
        • Portland Veterans Adm Med Ctr / Rsch & Education Grp
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Richmond AIDS Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Acyclovir (if patient is also receiving ddC, clinical monitoring should be more frequent).
  • Analgesics, antiemetics, antidiarrheal agents, or other necessary treatment for symptomatic therapy.
  • Interferons for maintenance therapy of Kaposi's sarcoma.
  • GM-CSF.

Required:

  • Prophylaxis against Pneumocystis carinii pneumonia (PCP) if their absolute CD4+ lymphocyte count is < 200 cells/mm3 at study entry. PCP prophylaxis for patient with CD4+ counts between 200 and 300 cells/mm3 is at discretion of patient's primary physician.
  • NOTE: There is potential interaction of ddI and dapsone.

Concurrent Treatment:

Allowed:

  • Transfusion, erythropoietin.

Patients must have the following:

  • Zidovudine (AZT) failure after having received a cumulative duration of at least 6 months.
  • AZT intolerance - rechallenge is not required for patients exhibiting = or > grade III cutaneous symptoms.
  • Diagnosis of AIDS or CD4+ = or < 300 cells/mm3 OR AIDS-defining illness other than Kaposi's sarcoma.
  • Willingness and ability to comply with protocol.
  • Informed consent must be obtained for all study participants in accordance with state law, local IRB requirements, and 45 CFR Part 46. AMENDED 11/19/90 to include assent by minors if they are physically able, in addition to consent by parents.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Any disorders for which the study drugs are contraindicated (didanosine (ddI)) is contraindicated in renal impairment, heart disease, receiving renal dialysis.
  • Active opportunistic infection.

Concurrent Medication:

Excluded:

  • Other antiretroviral agents.
  • Use of drugs associated with peripheral neuropathy or use of agents that may cause pancreatitis including intravenous pentamidine and alcohol should be restricted or avoided.

Concurrent Treatment:

Excluded:

  • Other concurrent antiretroviral clinical trials.

Patients with the following are excluded:

  • History of pancreatitis, peripheral neuropathy, uncontrolled seizures, renal impairment, heart disease, stage 2 or higher ADC.
  • Any other disorders for which the study drugs are contraindicated, i.e., ddI is contraindicated in renal impairment, patients receiving renal dialysis, and heart disease.
  • Receiving acute therapy for active AIDS defining opportunistic infection on enrollment.

Prior Medication:

Excluded:

  • Didanosine (ddI).
  • Dideoxycytidine (ddC) .

Excessive alcohol use that, in investigator's opinion, puts patient at risk of developing pancreatic disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Interventional Model: PARALLEL

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Bristol-Myers Squibb
Hoffmann-La Roche

Investigators

  • Study Chair: Kaplan C

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (ACTUAL)

September 1, 1992

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPCRA 002
  • 11554 (REGISTRY: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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