Clinical Trial: Dideoxycytidine ( Ro 24-2027 ) A Randomized, Open-Label, Comparative Study of Dideoxycytidine ( ddC ) versus Zidovudine ( AZT ) in Patients With AIDS or Advanced ARC Who Have Received Long-Term AZT Therapy.

This study has been completed.

Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Hoffmann-La Roche
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

To compare the effectiveness of zalcitabine ( dideoxycytidine; ddC ) therapy to zidovudine ( AZT ) in the treatment of AIDS or advanced AIDS related complex ( ARC ) in patients who have already received at least 1 year of AZT therapy and to define the safety profile. ddC has been shown to have an antiviral effect, and AZT is known to significantly decrease mortality and to reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. This may be due to the emergence of AZT resistant virus isolated from some patients who have been on long-term AZT therapy. These isolates were still sensitive to ddC. A study of long-term effectiveness of ddC in patients with AIDS or advanced ARC who have been on long-term AZT therapy is warranted because (1) ddC has antiviral activity, (2) there is no blood toxicity associated with taking ddC, and (3) the effectiveness of ddC in test tube studies does not seem to be diminished by decreased effectiveness of AZT.

Condition Treatment or Intervention Phase
HIV Infections
 Drug: Zidovudine
 Drug: Zalcitabine
Phase II

MedlinePlus related topics:  AIDS

Study Type: Interventional
Study Design: Treatment, Open Label

Further Study Details: 

Expected Total Enrollment:  320

ddC has been shown to have an antiviral effect, and AZT is known to significantly decrease mortality and to reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. This may be due to the emergence of AZT resistant virus isolated from some patients who have been on long-term AZT therapy. These isolates were still sensitive to ddC. A study of long-term effectiveness of ddC in patients with AIDS or advanced ARC who have been on long-term AZT therapy is warranted because (1) ddC has antiviral activity, (2) there is no blood toxicity associated with taking ddC, and (3) the effectiveness of ddC in test tube studies does not seem to be diminished by decreased effectiveness of AZT.

AMENDED: AZT will be administered orally every 4 or 5 hours. Patients in the second arm discontinue AZT and take ddC as two tablets every 8 hours. Duration of the study is 1 year with interim analysis done at 6 months after 75 percent enrollment and at end of the study. Original design: Patients with AIDS or advanced ARC who have been receiving at least 500 mg/day of AZT for at least 48 weeks are randomized to 1 of 2 treatment arms. Patients in the first treatment arm continue their current dose of AZT.

Eligibility

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Required:

  • Aerosolized pentamidine will be given, as tolerated for all patients, for Pneumocystis carinii pneumonia prophylaxis at a dose of 300 mg once every 4 weeks.

Allowed maintenance treatment with:

  • Pyrimethamine (= or < 75 mg/day).
  • Sulfadiazine (< 4 gl/day).
  • Amphotericin (1 mg/kg/day up to 5 days).
  • Fluconazole (400 mg/day).
  • Ketoconazole (400 mg/day).
  • Acyclovir (up to 12.4 mg/kg q8h IV for zoster or up to 4000 mg/day will be allowed PO with precautions - nausea and vomiting possible with doses > 1000 mg/day).
  • Ganciclovir (6 mg/kg/day).
  • Medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis, or Mycobacterium avium intracellulare.
  • Erythropoietin and megace as needed.
  • Isoniazid if patient has no peripheral neuropathy at study entry and is taking pyridoxine at least 50 mg/day concomitantly.
  • Phenytoin if patient has no peripheral neuropathy at study entry and has been stable on the drug for at least 3 months.

Patients must have had Pneumocystis carinii pneumonia (PCP) and no other AIDS defining opportunistic infection present when zidovudine (AZT) therapy was first initiated.

Patients must have:

  • Advanced AIDS related complex (ARC).
  • Antibody to HIV by federally licensed ELISA and confirmed by Western blot analysis.
  • Ability to give conformed consent.

Exclusion Criteria

Co-existing Condition: Patients are excluded who:

Concurrent Medication: Excluded:

  • Other experimental medications, including foscarnet, ribavirin, and fluconazole (prior to IND approval).
  • Other antiretroviral agents, biologic modifiers or corticosteroids.
  • Drugs that can cause peripheral neuropathy including phenytoin (under conditions not specifically allowed), hydralazine, metronidazole, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate.

Patients with the following are excluded:

Prior Medication: Excluded:

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

Active substance or alcohol abuse.


Location Information


California
      Mount Zion Med Ctr, San Francisco,  California,  94115,  United States

      Davies Med Ctr, San Francisco,  California,  94114,  United States

Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States

Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States

Louisiana
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States

Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States

New York
      Albany Med College / AIDS Treatment Ctr, Albany,  New York,  12203,  United States

Ohio
      Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati,  Ohio,  452670405,  United States

Pennsylvania
      Graduate Hosp, Philadelphia,  Pennsylvania,  19146,  United States

Texas
      N Texas Ctr for AIDS & Clin Rsch, Dallas,  Texas,  75219,  United States

More Information

Click here for more information about Zidovudine

Click here for more information about Zalcitabine

Publications

Fischl MA, Olson RM, Follansbee SE, Lalezari JP, Henry DH, Frame PT, Remick SC, Salgo MP, Lin AH, Nauss-Karol C, et al. Zalcitabine compared with zidovudine in patients with advanced HIV-1 infection who received previous zidovudine therapy. Ann Intern Med. 1993 May 15;118(10):762-9.

Gries JM, Troconiz IF, Verotta D, Jacobson M, Sheiner LB. A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex. Clin Pharmacol Ther. 1997 Jan;61(1):70-82.

Study ID Numbers:  ACTG 119; N3492B
Record last reviewed:  September 1992
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000678
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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