(Ro 24-2027) A Randomized, Double-Blind, Comparative Study of Dideoxycytidine (ddC) Versus Zidovudine (AZT) in Patients With AIDS or Advanced ARC

To show that zalcitabine (dideoxycytidine; ddC) is at least as effective as zidovudine (AZT) in the treatment of AIDS or advanced AIDS related complex (ARC), and also that ddC shows a different safety profile than AZT.

In clinical studies, ddC shows antiviral activity. Because of the antiviral activity, and because of the low incidence of mild, reversible neurotoxicity and absence of blood-related toxicity with low dose ddC therapy, a long-term Phase II/III study comparing ddC to AZT in patients with AIDS or advanced ARC is now warranted.

Study Overview

Status

Completed

Conditions

Detailed Description

In clinical studies, ddC shows antiviral activity. Because of the antiviral activity, and because of the low incidence of mild, reversible neurotoxicity and absence of blood-related toxicity with low dose ddC therapy, a long-term Phase II/III study comparing ddC to AZT in patients with AIDS or advanced ARC is now warranted.

After screening, physical examination and laboratory tests (within 14 days of entry) patients are randomized to one of two treatment groups. They receive either ddC plus an AZT placebo or AZT plus a ddC placebo. Because it is a blinded study, patients do not know which group they are in. Patients are evaluated weekly for the first 10 weeks and then biweekly thereafter.

Study Type

Interventional

Enrollment

600

Phase

  • Phase 2

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

    • California
      • Harbor City, California, United States, 90710
        • Kaiser Foundation Hosp
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Med Ctr
      • Sacramento, California, United States, 95817
        • UCD Med Ctr
      • San Francisco, California, United States, 94114
        • Davies Med Ctr
      • San Francisco, California, United States, 94115
        • Mount Zion Med Ctr
      • San Francisco, California, United States, 94121
        • San Francisco Veterans Administration Med Ctr
      • San Jose, California, United States, 95128
        • Santa Clara Valley Med Ctr
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown Univ Med Ctr
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Ctr for Special Immunology
      • Fort Myers, Florida, United States, 33901
        • Comprehensive Clinic / Dr Robert Schwartz
      • Miami, Florida, United States, 33125
        • Med Service
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • AIDS Research Consortium of Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • New England Med Ctr
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hosp
    • New Jersey
      • Newark, New Jersey, United States, 07102
        • Saint Michael's Med Ctr
    • New York
      • Albany, New York, United States, 12203
        • Albany Med College / AIDS Treatment Ctr
      • Brooklyn, New York, United States, 11220
        • Sunset Park Health Ctr - Lutheran Med Ctr
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Bowman Gray School of Medicine / North Carolina Baptist Hosp
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Univ Hosp of Cleveland / Case Western Reserve Univ
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19146
        • Graduate Hosp
    • Texas
      • Dallas, Texas, United States, 75219
        • N Texas Ctr for AIDS & Clin Rsch
      • Galveston, Texas, United States, 77550
        • Univ TX Galveston Med Branch
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Aerosolized pentamidine (300 mg once every 4 weeks) for Pneumocystis carinii pneumonia (PCP) prophylaxis.
  • Neuroleptics, benzodiazepines, or antidepressants if patient has been stable with chronic treatment > 1 month.
  • Low dose benzodiazepines or low dose antidepressants.
  • Drugs that are unlikely to cause increased toxicity with either study drug and are unlikely to cause peripheral neuropathy.
  • Drugs with little nephrotoxicity, hepatotoxicity, or cytotoxicity that the patient has been taking and tolerating well.
  • Acyclovir (up to 600 mg/kg/day) for up to 21 days.
  • Ketoconazole (up to 400 mg/day) Nystatin.
  • Low-dose acetaminophen or nonsteroidal anti-inflammatory agents.
  • Isoniazid if patient has no evidence of peripheral neuropathy at entry and if patient takes 50 mg/day pyridoxine concomitantly with isoniazid.
  • Allowed with interruption of study medication for up to 21 days per episode and for a total of 42 days for the study:
  • Drugs that could cause serious additive toxicity when coadministered with either study medication for treatment of an acute intercurrent illness or opportunistic infection, including:
  • Acyclovir (< 600 mg/day), fluconazole, systemic pentamidine, foscarnet, pyrimethamine, triple sulfa, ansamycin, ganciclovir, trimethoprim / sulfamethoxazole.

Patients must have a diagnosis of AIDS or advanced AIDS related complex (ARC). At least 20 percent of the patients must have a consistently positive serum HIV p24 antigen (= or > 70 pg/ml) as defined by the Abbott HIV antigen test, on two separate occasions at least 72 hours apart.

  • Patients found at screening to have a temperature > 38.5 degrees C should be evaluated for the possibility of an occult opportunistic or bacterial infection or neoplasm. If this complete evaluation reveals an infection, they can be entered. If this evaluation is unrevealing, they may be entered after evaluation is completed but while mycobacterial cultures are still pending. Patients with a history of unexplained temperatures > 38.5 degrees C should be evaluated as above and/or be afebrile (temperature < 38.0 degrees C) for 2 weeks prior to study entry.
  • Allowed: Kaposi's sarcoma not specifically excluded, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
  • Current positive venereal disease research label (VDRL) and fluorescent treponemal antibody (FTA) if treated as for asymptomatic neurosyphilis.

Prior Medication:

Allowed:

  • Drugs that cause peripheral neuropathy and drugs that could cause significant increased toxicity with zidovudine (AZT) or dideoxycytidine (ddC) including experimental drugs if therapy with these drugs is completed and patient is stable for 14 days.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Active AIDS defining opportunistic infection or other active intercurrent illness is excluded if ongoing treatment requires the use of excluded concomitant medication.
  • Patients with symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study, or with current neoplasms not specifically allowed.
  • Severe AIDS dementia complex defined by a score of < 23 on the Mini-Mental State Exam.
  • Signs, symptoms, or history of peripheral neuropathy.
  • Significant cardiac disease, defined as history of ventricular arrhythmias requiring medication, prior myocardial infarct, or history of angina or ischemia changes on ECG (electrocardiography).
  • Requiring > 2 weeks of acyclovir therapy at > 600 mg/day.
  • Current positive venereal disease research label (VDRL) and fluorescent treponemal antibody (FTA) not specifically allowed.
  • Significant liver disease.

Concurrent Medication:

Excluded:

  • Drugs that cause peripheral neuropathy:
  • chloramphenicol, cisplatinum, iodoquinol, dapsone, phenytoin, disulfiram, ethionamide, glutethimide, gold, hydralazine, ribavirin, metronidazole, vincristine, nitrofurantoin.
  • Drugs that could cause significant increased toxicity with zidovudine (AZT) or dideoxycytidine (ddC), including experimental drugs not specifically allowed.
  • Drugs that could cause seizures or changes in mental status or neurological examination.

Concurrent Treatment:

Excluded:

  • Transfusion dependency.

Patients with the following are excluded:

  • Active AIDS defining opportunistic infection or other active intercurrent illness if ongoing treatment requires use of excluded concomitant medication.
  • Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry, or current neoplasms not specifically allowed.
  • Severe AIDS dementia complex defined by a score of < 23 on the Mini-Mental State Exam.
  • Signs, symptoms, or history of peripheral neuropathy.
  • Unwilling or unable to sign informed consent.

Prior Medication:

Excluded:

  • Zidovudine (AZT), dideoxycytidine (ddC), or any other antiretroviral nucleoside analog.
  • Excluded within 90 days of study entry:
  • Any experimental drug including fluconazole, ganciclovir, foscarnet, erythropoietin, or ribavirin.

Excluded within 90 days of study entry:

  • Drugs that have caused significant nephrotoxicity or significant hepatotoxicity.
  • Drugs that could cause peripheral neuropathy including phenytoin, hydralazine, metronidazole, and nitrofurantoin.
  • Systemic corticosteroids or immunomodulators including interferon and interleukin.

Prior Treatment:

Excluded within 30 days of study entry:

  • Radiation therapy.

Active substance 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: Double

Collaborators and Investigators

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

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 Start

December 7, 2022

Primary Completion (Actual)

February 1, 1994

Study Completion

December 7, 2022

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 (Estimate)

March 14, 2011

Last Update Submitted That Met QC Criteria

March 11, 2011

Last Verified

December 1, 1994

More Information

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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