A Comparison of Zidovudine (AZT) Used Alone or in Combination With Didanosine (ddI) or Dideoxycytidine (ddC) in HIV-Infected Patients - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00001022

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Zidovudine Drug: Zalcitabine Drug: Didanosine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Double-Blind, Safety Study
Official Title:	A Randomized, Comparative Trial of Zidovudine (AZT) Versus AZT Plus Didanosine (ddI) Versus AZT Plus Dideoxycytidine (ddC) in HIV-Infected Patients

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine Didanosine Zalcitabine

U.S. FDA Resources

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

Estimated Enrollment:	1200
Study Completion Date:	August 2007

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.

Eligibility

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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001022

Locations

United States, California
Community Consortium of San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Denver CPCRA / Denver Public Hlth
Denver, Colorado, United States, 802044507
United States, Connecticut
Hill Health Corp
New Haven, Connecticut, United States, 06519
United States, Delaware
Wilmington Hosp / Med Ctr of Delaware
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Veterans Administration Med Ctr / Regional AIDS Program
Washington, District of Columbia, United States, 20422
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Illinois
AIDS Research Alliance - Chicago
Chicago, Illinois, United States, 60657
United States, Louisiana
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, United States, 70112
United States, Michigan
Henry Ford Hosp
Detroit, Michigan, United States, 48202
Comprehensive AIDS Alliance of Detroit
Detroit, Michigan, United States, 48201
United States, New Jersey
North Jersey Community Research Initiative
Newark, New Jersey, United States, 071032842
United States, New York
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
Clinical Directors Network of Region II
New York, New York, United States, 10011
Addiction Research and Treatment Corp
Brooklyn, New York, United States, 11201
United States, Oregon
Portland Veterans Adm Med Ctr / Rsch & Education Grp
Portland, Oregon, United States, 972109951
United States, Virginia
Richmond AIDS Consortium
Richmond, Virginia, United States, 23298

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	L Saravolatz
Study Chair:	D Winslow

More Information

Additional Information:

Click here for more information about Zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about Didanosine This link exits the ClinicalTrials.gov site

Publications:

Randall P. CPCRA 007: preliminary results of combination antiretroviral study. NIAID AIDS Agenda. 1996 Mar;:2. No abstract available.

[No authors listed] New trials reach same conclusion: two drugs are better than AZT alone. Aids Alert. 1995 Nov;10(11):133-6. No abstract available.

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)

[No authors listed] Ethnicity and treatment. PI Perspect. 1997 Jul;(No 22):15-6. No abstract available.

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)

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)

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)

James JS. AZT, ddI, and ddC combinations at FDA advisory hearing. Food and Drug Administration. AIDS Treat News. 1996 Apr 5;(no 244):6. No abstract available.

[No authors listed] Researchers are rethinking role of AZT in drug therapy. AIDS Policy Law. 1995 Oct 6;10(18):11. No abstract available.

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.

Randall P. CPCRA 007: preliminary results of combination antiretroviral study. NIAID AIDS Agenda. 1996 Mar;:2. No abstract available.

Study ID Numbers:	CPCRA 007
Study First Received:	November 2, 1999
Last Updated:	December 22, 2009
ClinicalTrials.gov Identifier:	NCT00001022 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Zalcitabine
Didanosine
Drug Therapy, Combination

Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections

Anti-HIV Agents
Immune System Diseases
Zalcitabine
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 08, 2010