Back to resultsA Comparison of Zidovudine (AZT) Used Alone or in Combination With Didanosine (ddI) or Dideoxycytidine (ddC) in HIV-Infected Patients
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Zalcitabine
Didanosine
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring Zalcitabine, Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine
Eligibility Criteria
Inclusion Criteria Required: Documented HIV infection OR working diagnosis of HIV OR evidence of idiopathic suppression with an AIDS-defining opportunistic infection or malignancy (except Kaposi's sarcoma). CD4+ cell count = or < 200/mm3 or = or < 15 percent of total lymphocyte count within previous 90 days OR history of AIDS-defining opportunistic infection. Current PCP prophylaxis. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Symptoms of pancreatitis or peripheral neuropathy of grade 2 or worse. Requirement for acute therapy for any active AIDS-defining opportunistic infection or systemic chemotherapy for malignancy. Stage 2 or worse (moderate) AIDS Dementia Complex. Other disorders or conditions for which the study drugs are contraindicated or that may prevent adequate compliance with study therapy. Concurrent Medication: Excluded: Acute therapy for active AIDS-defining opportunistic infection. Systemic chemotherapy for malignancy. Antiretroviral therapy other than that provided by this study. Patients with the following prior conditions are excluded: History of pancreatitis or peripheral neuropathy of grade 2 or worse. History of intolerance to the study drugs at entry doses and/or frequencies. History of phenylketonuria.
Sites / Locations
- Community Consortium of San Francisco
- Denver CPCRA / Denver Public Hlth
- Hill Health Corp
- Wilmington Hosp / Med Ctr of Delaware
- Veterans Administration Med Ctr / Regional AIDS Program
- AIDS Research Consortium of Atlanta
- AIDS Research Alliance - Chicago
- Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
- Comprehensive AIDS Alliance of Detroit
- Henry Ford Hosp
- North Jersey Community Research Initiative
- Addiction Research and Treatment Corp
- Clinical Directors Network of Region II
- Harlem AIDS Treatment Group / Harlem Hosp Ctr
- Portland Veterans Adm Med Ctr / Rsch & Education Grp
- Richmond AIDS Consortium
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00001022
First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT00001022
Brief Title
A Comparison of Zidovudine (AZT) Used Alone or in Combination With Didanosine (ddI) or Dideoxycytidine (ddC) in HIV-Infected Patients
Official Title
A Randomized, Comparative Trial of Zidovudine (AZT) Versus AZT Plus Didanosine (ddI) Versus AZT Plus Dideoxycytidine (ddC) in HIV-Infected Patients
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
December 1995 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
5. Study Description
Brief Summary
Primary: To compare the efficacy of zidovudine ( AZT ) given alone versus AZT plus didanosine ( ddI ) versus AZT plus zalcitabine ( dideoxycytidine; ddC ) in delaying the occurrence of AIDS-related conditions in HIV-infected patients.
Secondary: To compare the frequency and severity of adverse experiences in the three regimens. To compare the mortality rates in the three regimens. To compare the effects of antiretroviral regimens on CD4+ cell levels.
Studies have indicated that maintenance therapy with AZT over extended periods may be limited by dose-dependent toxicity, primarily myelosuppression, and by the emergence of drug-resistant HIV strains. It is anticipated that the combination of AZT with either ddI or ddC may promote higher antiviral efficacy, with acceptable toxicity and less likelihood of development of drug-resistant strains, than AZT alone.
Detailed Description
Studies have indicated that maintenance therapy with AZT over extended periods may be limited by dose-dependent toxicity, primarily myelosuppression, and by the emergence of drug-resistant HIV strains. It is anticipated that the combination of AZT with either ddI or ddC may promote higher antiviral efficacy, with acceptable toxicity and less likelihood of development of drug-resistant strains, than AZT alone.
Approximately 1200 patients are randomized in a 2:1:1:2 ratio to one of the following four treatment arms: AZT plus ddI, AZT plus ddI placebo, AZT plus ddC placebo, and AZT plus ddC. Average follow-up is 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Zalcitabine, Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Masking
Double
Enrollment
1200 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Zalcitabine
Intervention Type
Drug
Intervention Name(s)
Didanosine
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Required:
Documented HIV infection OR working diagnosis of HIV OR evidence of idiopathic suppression with an AIDS-defining opportunistic infection or malignancy (except Kaposi's sarcoma).
CD4+ cell count = or < 200/mm3 or = or < 15 percent of total lymphocyte count within previous 90 days OR history of AIDS-defining opportunistic infection.
Current PCP prophylaxis.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms and conditions are excluded:
Symptoms of pancreatitis or peripheral neuropathy of grade 2 or worse.
Requirement for acute therapy for any active AIDS-defining opportunistic infection or systemic chemotherapy for malignancy.
Stage 2 or worse (moderate) AIDS Dementia Complex.
Other disorders or conditions for which the study drugs are contraindicated or that may prevent adequate compliance with study therapy.
Concurrent Medication:
Excluded:
Acute therapy for active AIDS-defining opportunistic infection.
Systemic chemotherapy for malignancy.
Antiretroviral therapy other than that provided by this study.
Patients with the following prior conditions are excluded:
History of pancreatitis or peripheral neuropathy of grade 2 or worse.
History of intolerance to the study drugs at entry doses and/or frequencies.
History of phenylketonuria.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
L Saravolatz
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
D Winslow
Official's Role
Study Chair
Facility Information:
Facility Name
Community Consortium of San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Denver CPCRA / Denver Public Hlth
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Hill Health Corp
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Wilmington Hosp / Med Ctr of Delaware
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19899
Country
United States
Facility Name
Veterans Administration Med Ctr / Regional AIDS Program
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
AIDS Research Consortium of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
AIDS Research Alliance - Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Comprehensive AIDS Alliance of Detroit
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hosp
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
North Jersey Community Research Initiative
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Addiction Research and Treatment Corp
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
Clinical Directors Network of Region II
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Harlem AIDS Treatment Group / Harlem Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Portland Veterans Adm Med Ctr / Rsch & Education Grp
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Richmond AIDS Consortium
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11362921
Citation
New trials reach same conclusion: two drugs are better than AZT alone. AIDS Alert. 1995 Nov;10(11):133-6.
Results Reference
background
Citation
Saravolatz LD, Collins G, Hodges D, Winslow D, Pettinelli C. A randomized, comparative trial of ZDV versus ZDV plus ddI versus ZDV plus ddC in persons with CD4 cell counts of less than 200/mm3. Int Conf AIDS. 1996 Jul 7-12;11(1):21 (abstract no MoB291)
Results Reference
background
PubMed Identifier
11364573
Citation
Ethnicity and treatment. Proj Inf Perspect. 1997 Jul;(22):15-6.
Results Reference
background
Citation
Besch CL, Morse E, Simon P, Hodges J, Franchino B. Preliminary results of a compliance study within CPCRA 007 combination nucleoside study (NuCombo). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:111 (abstract no 254)
Results Reference
background
Citation
Mayers D, Saravolatz L, Winslow D, Jagodzinski L, Collins G, Hodges D, Pettinelli C, Weislow O, Stein D. Viral burden measurements in CPCRA 007. Int Conf AIDS. 1996 Jul 7-12;11(Program Supplement):16 (abstract no ThB911)
Results Reference
background
Citation
Kumi J, Collins G, Saravolatz L. Does ethnicity influence the efficacy and toxicity of combination versus monotherapy with nucleosides in AIDS patients? Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:166 (abstract no 547)
Results Reference
background
PubMed Identifier
11363307
Citation
James JS. AZT, ddI, and ddC combinations at FDA advisory hearing. Food and Drug Administration. AIDS Treat News. 1996 Apr 5;(no 244):6.
Results Reference
background
PubMed Identifier
11362821
Citation
Researchers are rethinking role of AZT in drug therapy. AIDS Policy Law. 1995 Oct 6;10(18):11.
Results Reference
background
PubMed Identifier
8813040
Citation
Saravolatz LD, Winslow DL, Collins G, Hodges JS, Pettinelli C, Stein DS, Markowitz N, Reves R, Loveless MO, Crane L, Thompson M, Abrams D. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. 1996 Oct 10;335(15):1099-106. doi: 10.1056/NEJM199610103351503.
Results Reference
background
PubMed Identifier
11363796
Citation
Randall P. CPCRA 007: preliminary results of combination antiretroviral study. NIAID AIDS Agenda. 1996 Mar:2.
Results Reference
background
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A Comparison of Zidovudine (AZT) Used Alone or in Combination With Didanosine (ddI) or Dideoxycytidine (ddC) in HIV-Infected Patients
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