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

HIV Infections Clinical Trial

Official title:

A Randomized, Comparative Trial of Zidovudine (AZT) Versus AZT Plus Didanosine (ddI) Versus AZT Plus Dideoxycytidine (ddC) in HIV-Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001022
• Other study ID #: CPCRA 007
• Secondary ID: 11559
• Status: Completed
• Phase: Phase 3
• Est. completion date: December 1995

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: December 1995
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Zidovudine

• Zalcitabine

• Didanosine

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Addiction Research and Treatment Corp	Brooklyn	New York
United States	AIDS Research Alliance - Chicago	Chicago	Illinois
United States	Denver CPCRA / Denver Public Hlth	Denver	Colorado
United States	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan
United States	Henry Ford Hosp	Detroit	Michigan
United States	Hill Health Corp	New Haven	Connecticut
United States	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana
United States	Clinical Directors Network of Region II	New York	New York
United States	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York
United States	North Jersey Community Research Initiative	Newark	New Jersey
United States	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon
United States	Richmond AIDS Consortium	Richmond	Virginia
United States	Community Consortium of San Francisco	San Francisco	California
United States	Veterans Administration Med Ctr / Regional AIDS Program	Washington	District of Columbia
United States	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View 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. — View 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)

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. — View Citation

Randall P. CPCRA 007: preliminary results of combination antiretroviral study. NIAID AIDS Agenda. 1996 Mar:2. — View Citation

Researchers are rethinking role of AZT in drug therapy. AIDS Policy Law. 1995 Oct 6;10(18):11. — View 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)

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. — View Citation