A Clinical Trial of Alternating and Intermittent Regimens of 2',3'-Dideoxycytidine and 3'-Azido-3'-Deoxythymidine in the Treatment of Patients With AIDS and Advanced ARC

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine if alternating zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) (first one and then the other) or intermittent therapy (1 week of drug then 1 week off) will lessen the toxic effects of either drug alone, while still inhibiting HIV (the AIDS virus) in patients with AIDS or AIDS related complex.

AZT extends the survival of some patients with AIDS, and both AZT and ddC are known to inhibit the growth of HIV. When AZT or ddC is given continuously over a prolonged period of time, toxic effects occur that are not found when the drugs are given for 4 - 6 weeks. It is hoped that by alternating the drugs or by giving one drug intermittently, the toxic effects can be decreased without lowering the therapeutic effectiveness of the drugs.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AZT extends the survival of some patients with AIDS, and both AZT and ddC are known to inhibit the growth of HIV. When AZT or ddC is given continuously over a prolonged period of time, toxic effects occur that are not found when the drugs are given for 4 - 6 weeks. It is hoped that by alternating the drugs or by giving one drug intermittently, the toxic effects can be decreased without lowering the therapeutic effectiveness of the drugs.

Patients will be assigned to 1 of 7 treatment groups. Both AZT and ddC will be given by mouth every 4 hours. One group will take AZT continuously for 52 weeks. One group will alternate 1 week of AZT with a week with no drug for 48 weeks and another group will alternate 1 week of ddC with a week of no drug for 48 weeks. Other groups will alternate AZT and either low-dose or high-dose ddC on a weekly basis or a monthly basis for 48 weeks. Patients will be seen weekly for the first 8 weeks of study and less often thereafter. Blood samples will be withdrawn frequently and evaluated for possible changes in the immune system, toxic effects, and possible changes in the amount of HIV in the blood. Lumbar punctures and skin biopsies will also be performed.

AMENDED: All patients receiving continuous AZT will be switched to a lower dose of AZT if they have not already been switched. This is in accordance with results of NIAID ACTG 002, 016, and 019 which demonstrate that this dose of AZT delays progression of HIV symptoms.

Study Type

Interventional

Enrollment

112

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
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University CRS

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 (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Encouraged though not required:

  • Inhaled pentamidine as prophylaxis for Pneumocystis carinii pneumonia (PCP).
  • Allowed:
  • AL-721 use is discouraged but not prohibited.
  • Use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents should be minimized, with continuous use for > 72 hours discouraged.
  • Acute therapy (7 days) with oral acyclovir.
  • Acute therapy with ketoconazole.

Concurrent Treatment:

Allowed:

  • Up to 4 units of packed red blood cells for hemoglobin toxicity.

All patients must have the following:

  • A consistently positive serum HIV p24 antigen = or > 70 pg/ml, defined by the Abbott HIV antigen test, on two occasions. The tests must be within 1 month of study entry, separated by at least 72 hours, and the last must be within 2 weeks of starting therapy. Any negative antigen test during the period will exclude the patient from the study.
  • A positive antibody to HIV confirmed by any federally licensed ELISA test kit.
  • Patients in group A must have AIDS related complex (ARC) as defined by the documented presence of at least one of the following:
  • Recurrent oral candidiasis.
  • Hairy leukoplakia.
  • History of herpes zoster.
  • Temperature > 38.5 degrees C with or without night sweats, persisting for > 14 consecutive days or > 15 days in a 30-day interval prior to study entry.
  • Weight loss of > 15 lbs. or 10 percent of body weight noted in a 120-day period prior to study entry.
  • Diarrhea defined as = or > 3 liquid stools per day, persisting for > 30 days prior to study entry without definable cause.
  • Patients in group B must have CDC-defined AIDS not requiring systemic maintenance chemotherapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Transfusion dependence requiring 2 units of blood more than once per month.
  • Significant malabsorption (> 10 percent weight loss within the past 3 months with serum carotene < 75 IU/ml or vitamin A < 74 IU/ml).
  • Significant cardiac or liver disease.
  • Significant neurologic abnormalities defined by any one of the following:
  • A significant abnormality on the ddC Neuropathy Targeted Symptom Questionnaire defined as a symptom score > 4 (moderate severity) in any one of six categories or a score > 2 (mild severity) in any two of six categories.
  • Moderate abnormalities on standardized neurologic exam.
  • Any severe abnormality (a value = or > 4.0) on standardized 4-arm quantitative sensory testing of vibration threshold.
  • Diabetes, renal failure, or alcoholism.
  • Dose-limiting or transfusion-requiring toxicity during a previous course of zidovudine therapy.
  • History of idiopathic thrombocytopenic purpura.
  • Requirement for prolonged acyclovir therapy. Patients in group A must not have the following:
  • Opportunistic infection or malignancy fulfilling the CDC definition of AIDS.
  • Neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. Patients in group B must not have the following:
  • Active opportunistic infection or AIDS-defining opportunistic infection requiring ongoing systemic therapy and/or prophylaxis other than inhaled pentamidine for Pneumocystis carinii pneumonia prophylaxis.
  • Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry.
  • Concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.

Concurrent Medication:

Excluded:

  • Neurotoxic drugs.
  • Prolonged acyclovir therapy.
  • Antineoplastic therapy.
  • Systemic therapy and/or prophylaxis for an AIDS-defining opportunistic infection, other than inhaled pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.
  • Other antiretroviral agents, immunomodulators, or systemic corticosteroids.
  • Other experimental medication.

Concurrent Treatment:

Excluded:

  • Transfusion dependency (requiring 2 units of blood more than once per month).

Prior Medication:

Excluded:

  • Antiretroviral agents within 60 days of study entry.
  • Biologic modifiers or corticosteroids within 30 days prior to study entry.
  • Dideoxycytidine (ddC).

Prior Treatment:

Excluded:

  • Blood transfusion within 2 weeks of entry.

Any negative HIV p24 antigen test during the month prior to entry will exclude the patient from the study.

Active drug or alcohol abuse.

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
  • Masking: None (Open Label)

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

Hoffmann-La Roche

Investigators

  • Study Chair: G Skowron

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, 1991

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 3, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 047
  • 11021 (Registry Identifier: 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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