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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

  Show 40 Study Locations
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:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae 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 November 27, 2014