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.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000678
First received: November 2, 1999
Last updated: March 11, 2011
Last verified: September 1992
  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 Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Zalcitabine
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 320
Primary Completion Date: July 1992 (Final data collection date for primary outcome measure)
Detailed Description:

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 older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

  • Have had zidovudine (AZT) therapy interrupted for > 30 consecutive days at any time during AZT therapy or have been off AZT for > 90 days total.
  • Have had AZT therapy interrupted for "recurrent" grade 4 toxicity, defined as > one episode of the same grade 4 toxicity after dose interruption or attenuation.
  • Have visceral or extensive Kaposi's sarcoma requiring therapy or any other malignancy requiring therapy.
  • Have a history of peripheral neuropathy.

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:

  • History of peripheral neuropathy or moderate to severe peripheral neuropathy as defined by the combination of signs or symptoms of peripheral neuropathy and findings indicative of peripheral neuropathy on the standardized neurologic exam.
  • Active opportunistic infection.
  • Participation in another research treatment study.

Prior Medication:

Excluded:

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

Active substance or alcohol abuse.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000678

Locations
United States, California
Davies Med Ctr
San Francisco, California, United States, 94114
Mount Zion Med Ctr
San Francisco, California, United States, 94115
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Louisiana
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, New York
Albany Med College / AIDS Treatment Ctr
Albany, New York, United States, 12203
United States, Ohio
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Graduate Hosp
Philadelphia, Pennsylvania, United States, 19146
United States, Texas
N Texas Ctr for AIDS & Clin Rsch
Dallas, Texas, United States, 75219
Sponsors and Collaborators
Hoffmann-La Roche
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000678     History of Changes
Other Study ID Numbers: ACTG 119, N3492B
Study First Received: November 2, 1999
Last Updated: March 11, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Zalcitabine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014