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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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Zalcitabine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Zalcitabine, Antiviral Agents, Zidovudine

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • USC CRS
  • UCLA CARE Center CRS
  • UCSD Maternal, Child, and Adolescent HIV CRS
  • Ucsd, Avrc Crs
  • Ucsf Aids Crs
  • Harbor-UCLA Med. Ctr. CRS
  • University of Colorado Hospital CRS
  • Univ. of Miami AIDS CRS
  • Northwestern University CRS
  • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Tulane Hemophilia Treatment Ctr.
  • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
  • Johns Hopkins Adult AIDS CRS
  • Massachusetts General Hospital ACTG CRS
  • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
  • Bmc Actg Crs
  • Beth Israel Deaconess - East Campus A0102 CRS
  • Beth Israel Deaconess Med. Ctr., ACTG CRS
  • Brigham and Women's Hosp., Div. of Infectious Disease
  • University of Minnesota, ACTU
  • St. Louis ConnectCare, Infectious Diseases Clinic
  • Washington U CRS
  • NJ Med. School CRS
  • SUNY - Buffalo, Erie County Medical Ctr.
  • NYU Med. Ctr., Dept. of Medicine
  • Cornell University A2201
  • Memorial Sloan-Kettering Cancer Ctr.
  • Beth Israel Med. Ctr. (Mt. Sinai)
  • NY Univ. HIV/AIDS CRS
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • Carolinas HealthCare System, Carolinas Med. Ctr.
  • Duke Univ. Med. Ctr. Adult CRS
  • Regional Center for Infectious Disease, Wendover Medical Center CRS
  • Univ. of Cincinnati CRS
  • Case CRS
  • The Ohio State Univ. AIDS CRS
  • Pitt CRS
  • University of Washington AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00000651
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1993 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche, Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Zalcitabine, Antiviral Agents, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Masking
Double
Enrollment
750 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Zalcitabine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M Fischl
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
A Collier
Official's Role
Study Chair
Facility Information:
Facility Name
USC CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSD Maternal, Child, and Adolescent HIV CRS
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Ucsd, Avrc Crs
City
San Diego
State/Province
California
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
Country
United States
Facility Name
Harbor-UCLA Med. Ctr. CRS
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Tulane Hemophilia Treatment Ctr.
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
HMS - Children's Hosp. Boston, Div. of Infectious Diseases
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Bmc Actg Crs
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Beth Israel Deaconess Med. Ctr., ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Brigham and Women's Hosp., Div. of Infectious Disease
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Minnesota, ACTU
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St. Louis ConnectCare, Infectious Diseases Clinic
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
NJ Med. School CRS
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
NYU Med. Ctr., Dept. of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell University A2201
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Beth Israel Med. Ctr. (Mt. Sinai)
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Carolinas HealthCare System, Carolinas Med. Ctr.
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Regional Center for Infectious Disease, Wendover Medical Center CRS
City
Greensboro
State/Province
North Carolina
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Pitt CRS
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8780079
Citation
Blum AS, Dal Pan GJ, Feinberg J, Raines C, Mayjo K, Cornblath DR, McArthur JC. Low-dose zalcitabine-related toxic neuropathy: frequency, natural history, and risk factors. Neurology. 1996 Apr;46(4):999-1003. doi: 10.1212/wnl.46.4.999.
Results Reference
background
PubMed Identifier
7552481
Citation
Fichtenbaum CJ, Clifford DB, Powderly WG. Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):169-74. doi: 10.1097/00042560-199510020-00009.
Results Reference
background
Citation
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)
Results Reference
background
Citation
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)
Results Reference
background
PubMed Identifier
7811541
Citation
Johnson VA. Combination therapy: more effective control of HIV type 1? AIDS Res Hum Retroviruses. 1994 Aug;10(8):907-12. doi: 10.1089/aid.1994.10.907.
Results Reference
background
PubMed Identifier
7985892
Citation
Fischl MA, Stanley K, Collier AC, Arduino JM, Stein DS, Feinberg JE, Allan JD, Goldsmith JC, Powderly WG. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. Ann Intern Med. 1995 Jan 1;122(1):24-32. doi: 10.7326/0003-4819-122-1-199501010-00004.
Results Reference
background
PubMed Identifier
9342254
Citation
Spino C, Kahn JO, Dolin R, Phair JP. Predictors of survival in HIV-infected persons with 50 or fewer CD4 cells/mm3. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):346-55. doi: 10.1097/00042560-199708150-00004.
Results Reference
background
PubMed Identifier
10843534
Citation
Zackin RA, Clark RA, Currier JS, Mildvan D. Predictive markers of HIV-related weight loss and determination of differences between populations with weight loss stratified by opportunistic processes. J Acquir Immune Defic Syndr. 1999 Oct 1;22(2):189-93. doi: 10.1097/00126334-199910010-00012.
Results Reference
background

Learn more about this trial

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

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