A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000651
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

To evaluate the safety of zalcitabine (dideoxycytidine; ddC) alone and in combination with zidovudine (AZT) versus AZT alone when administered to asymptomatic patients with a CD4 count = or < 200 cells/mm3 and symptomatic patients with a CD4 count = or < 300 cells/mm3. To compare the effectiveness of ddC alone and in combination with AZT versus AZT alone.

ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and 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. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Zalcitabine
Phase 3

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

Resource links provided by NLM:


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

Estimated Enrollment: 750
Study Completion Date: May 1993
Detailed Description:

ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and 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. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.

Patients are randomly assigned to 1 of 3 treatment groups. In study arm 1, patients receive AZT plus ddC placebo. In study arm 2, patients receive ddC plus AZT placebo capsules. In study arm 3, patients receive ddC plus AZT. Patients are seen every other week for first 8 weeks and monthly thereafter. Patients are stratified by HIV disease status, length of time receiving AZT, and systemic or local Pneumocystis carinii pneumonia (PCP) prophylaxis. Patients who reach a clinical AIDS-defining endpoint are offered open-label combination therapy.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • Zidovudine (AZT) = or > 300 mg/day for 6 weeks prior to study entry.

Allowed:

  • Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), candidiasis, and herpes.
  • 21 day course of adjuvant systemic corticosteroids for moderate to severe PCP.
  • Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, ganciclovir, or 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.
  • 14 day course of metronidazole.
  • Erythropoietin and megace if clinically indicated.
  • Isoniazid if patient has no peripheral neuropathy at entry and is taking pyridoxine = or > 50 mg/day concomitantly.
  • Phenytoin if patient has < grade 2 peripheral neuropathy at entry and has been stable on phenytoin = or > 3 months.

Patients must have:

  • Ability and willingness to give informed consent.
  • Written informed consent from a parent or guardian if < 18 years old.
  • Been tolerating zidovudine (AZT) therapy.
  • Diagnosis of HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Kaposi's sarcoma or other malignancy requiring therapy.
  • Active opportunistic infections.
  • Peripheral neuropathy as manifested by complaints of moderate pain, burning, numbness, or tingling in hands/arms or feet/legs; moderate sensory deficit in the upper or lower extremities; or motor weakness in the upper or lower extremities.

Concurrent Medication:

Excluded:

  • Other experimental medications.
  • Other anti-HIV drugs.
  • Biologic response modifiers.
  • Cytotoxic chemotherapy.
  • Drugs that could cause peripheral neuropathy including phenytoin not specifically allowed, hydralazine, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate.

Concurrent Treatment:

Excluded:

  • Radiation therapy.

Patients with the following are excluded:

  • Active opportunistic infection. Must have ended acute therapy at least 14 days prior to study entry.
  • Peripheral neuropathy = or > grade 2.
  • History of intolerance to 500 to 600 mg/day of zidovudine (AZT) as manifested by the same recurrent grade 3 toxicity requiring dose interruptions and dose reductions to < 500 mg/day or any prior grade 4 toxicity.
  • Prior development of peripheral neuropathy on ddI = or > grade 2.

Prior Medication:

Excluded:

  • Dideoxycytidine (ddC).

Required:

  • Zidovudine (AZT) for total of at least 24 weeks; and included within that time period, AZT = or > 300 mg/day for 6 weeks prior to the study entry.
  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: NCT00000651

  Hide Study Locations
Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
USC CRS
Los Angeles, California, United States, 90033
UCSD Maternal, Child, and Adolescent HIV CRS
San Diego, California, United States, 92103
Ucsd, Avrc Crs
San Diego, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Hemophilia Treatment Ctr.
New Orleans, Louisiana, United States
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
Boston, Massachusetts, United States, 02115
Brigham and Women's Hosp., Div. of Infectious Disease
Boston, Massachusetts, United States
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St Louis, Missouri, United States
United States, New Jersey
NJ Med. School CRS
Newark, New Jersey, United States, 07103
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
NYU Med. Ctr., Dept. of Medicine
New York, New York, United States, 10016
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 10029
Cornell University A2201
New York, New York, United States, 10021
NY Univ. HIV/AIDS CRS
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, United States
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Case CRS
Cleveland, Ohio, United States, 44106
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Hoffmann-La Roche
Glaxo Wellcome
Investigators
Study Chair: M Fischl
Study Chair: A Collier
  More Information

Additional Information:
Publications:
Fischl M, Collier A, Stanley K, Ardunio JM, Kazial K, Stein D. The safety and efficacy of zidovudine (ZDV) and zalcitabine (ddC) or ddC alone versus ZDV. ACTG 155 Team of the NIAID. Int Conf AIDS. 1993 Jun 6-11;9(1):68 (abstract no WS-B25-1)
Keruly J, Kendig N, Feinberg J, Cotton S, Biggs M, Benjamin Y, Francis H, Wade W, Coplin M, Bartlett J. A model for conducting AIDS clinical trials in a state correctional system. Int Conf AIDS. 1992 Jul 19-24;8(2):B236 (abstract no PoB 3873)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000651     History of Changes
Other Study ID Numbers: ACTG 155, 11130
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Antiviral Agents
Zidovudine

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

ClinicalTrials.gov processed this record on September 18, 2014