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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00001022
• Collaborator: (none)
• Enrollment: 1,200
• Locations: 16
• Patients Per Site: 75

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine; Drug: Zalcitabine; Drug: Didanosine	Phase 3

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.

Study Design

• Study Type: Interventional
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomized, Comparative Trial of Zidovudine (AZT) Versus AZT Plus Didanosine (ddI) Versus AZT Plus Dideoxycytidine (ddC) in HIV-Infected Patients
• Actual Study Completion Date: Dec 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Community Consortium of San Francisco	San Francisco	California	United States	94110
2	Denver CPCRA / Denver Public Hlth	Denver	Colorado	United States	80204
3	Hill Health Corp	New Haven	Connecticut	United States	06519
4	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware	United States	19899
5	Veterans Administration Med Ctr / Regional AIDS Program	Washington	District of Columbia	United States	20422
6	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
7	AIDS Research Alliance - Chicago	Chicago	Illinois	United States	60657
8	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana	United States	70112
9	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan	United States	48201
10	Henry Ford Hosp	Detroit	Michigan	United States	48202
11	North Jersey Community Research Initiative	Newark	New Jersey	United States	07103
12	Addiction Research and Treatment Corp	Brooklyn	New York	United States	11201
13	Clinical Directors Network of Region II	New York	New York	United States	10011
14	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York	United States	10037
15	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon	United States	97210
16	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,

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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)
• Ethnicity and treatment. Proj Inf Perspect. 1997 Jul;(22):15-6.
• James JS. AZT, ddI, and ddC combinations at FDA advisory hearing. Food and Drug Administration. AIDS Treat News. 1996 Apr 5;(no 244):6.
• 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)
• 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)
• New trials reach same conclusion: two drugs are better than AZT alone. AIDS Alert. 1995 Nov;10(11):133-6.
• Randall P. CPCRA 007: preliminary results of combination antiretroviral study. NIAID AIDS Agenda. 1996 Mar:2.
• Researchers are rethinking role of AZT in drug therapy. AIDS Policy Law. 1995 Oct 6;10(18):11.
• 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)
• 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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00001022
• Other Study ID Numbers: CPCRA 007; 11559
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 4, 2021
• Last Verified: Oct 1, 2021

• 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: HIV Infections; Zidovudine; Didanosine; Zalcitabine

Study Results

No Results Posted as of Nov 4, 2021