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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Zidovudine (Drug); Zalcitabine (Drug); Didanosine (Drug)

Phase: Phase 3

Status: Completed

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

Official(s) and/or principal investigator(s):
L Saravolatz, Study Chair
D Winslow, Study Chair

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.

Clinical Details

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

Study design: Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment

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

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

Community Consortium of San Francisco, San Francisco, California 94110, United States

Denver CPCRA / Denver Public Hlth, Denver, Colorado 80204, United States

Hill Health Corp, New Haven, Connecticut 06519, United States

Wilmington Hosp / Med Ctr of Delaware, Wilmington, Delaware 19899, United States

Veterans Administration Med Ctr / Regional AIDS Program, Washington, District of Columbia 20422, United States

AIDS Research Consortium of Atlanta, Atlanta, Georgia 30308, United States

AIDS Research Alliance - Chicago, Chicago, Illinois 60657, United States

Louisiana Comm AIDS Rsch Prog / Tulane Univ Med, New Orleans, Louisiana 70112, United States

Comprehensive AIDS Alliance of Detroit, Detroit, Michigan 48201, United States

Henry Ford Hosp, Detroit, Michigan 48202, United States

North Jersey Community Research Initiative, Newark, New Jersey 07103, United States

Addiction Research and Treatment Corp, Brooklyn, New York 11201, United States

Clinical Directors Network of Region II, New York, New York 10011, United States

Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York, New York 10037, United States

Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland, Oregon 97210, United States

Richmond AIDS Consortium, Richmond, Virginia 23298, United States

Additional Information

Click here for more information about Zidovudine

Click here for more information about Didanosine

Related publications:

New trials reach same conclusion: two drugs are better than AZT alone. AIDS Alert. 1995 Nov;10(11):133-6.

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)

Ethnicity and treatment. Proj Inf Perspect. 1997 Jul;(22):15-6.

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.

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

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.


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