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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.

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
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, Drug Evaluation, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine

Eligibility Criteria

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

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.

Sites / Locations

  • Davies Med Ctr
  • Mount Zion Med Ctr
  • Univ of Miami School of Medicine
  • Indiana Univ Hosp
  • Tulane Univ School of Medicine
  • Johns Hopkins Hosp
  • Albany Med College / AIDS Treatment Ctr
  • Holmes Hosp / Univ of Cincinnati Med Ctr
  • Graduate Hosp
  • N Texas Ctr for AIDS & Clin Rsch

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
March 11, 2011
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00000678
Brief 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.
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 1992
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
July 1992 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Zalcitabine, Drug Evaluation, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
320 (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: 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.
Facility Information:
Facility Name
Davies Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94114
Country
United States
Facility Name
Mount Zion Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Univ of Miami School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Tulane Univ School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Johns Hopkins Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Albany Med College / AIDS Treatment Ctr
City
Albany
State/Province
New York
ZIP/Postal Code
12203
Country
United States
Facility Name
Holmes Hosp / Univ of Cincinnati Med Ctr
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Graduate Hosp
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19146
Country
United States
Facility Name
N Texas Ctr for AIDS & Clin Rsch
City
Dallas
State/Province
Texas
ZIP/Postal Code
75219
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8097082
Citation
Fischl MA, Olson RM, Follansbee SE, Lalezari JP, Henry DH, Frame PT, Remick SC, Salgo MP, Lin AH, Nauss-Karol C, Lieberman J, Soo W. 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. doi: 10.7326/0003-4819-118-10-199305150-00002.
Results Reference
background
PubMed Identifier
9024175
Citation
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. doi: 10.1016/S0009-9236(97)90183-1.
Results Reference
background

Learn more about this 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.

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