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

NCT00001022 | Completed Phase 3

• 2 other identifiers: CPCRA 00711559
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 16

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.

Conditions

HIV Infections

Keywords

Zalcitabine; Didanosine; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Zidovudine

Interventions

Zidovudine DRUG

Zalcitabine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (16)

Community Consortium of San Francisco

San Francisco, California, 94110, United States

Location

Denver CPCRA / Denver Public Hlth

Denver, Colorado, 80204, United States

Location

Hill Health Corp

New Haven, Connecticut, 06519, United States

Location

Wilmington Hosp / Med Ctr of Delaware

Wilmington, Delaware, 19899, United States

Location

Veterans Administration Med Ctr / Regional AIDS Program

Washington D.C., District of Columbia, 20422, United States

Location

AIDS Research Consortium of Atlanta

Atlanta, Georgia, 30308, United States

Location

AIDS Research Alliance - Chicago

Chicago, Illinois, 60657, United States

Location

Louisiana Comm AIDS Rsch Prog / Tulane Univ Med

New Orleans, Louisiana, 70112, United States

Location

Comprehensive AIDS Alliance of Detroit

Detroit, Michigan, 48201, United States

Location

Henry Ford Hosp

Detroit, Michigan, 48202, United States

Location

North Jersey Community Research Initiative

Newark, New Jersey, 07103, United States

Location

Addiction Research and Treatment Corp

Brooklyn, New York, 11201, United States

Location

Clinical Directors Network of Region II

New York, New York, 10011, United States

Location

Harlem AIDS Treatment Group / Harlem Hosp Ctr

New York, New York, 10037, United States

Location

Portland Veterans Adm Med Ctr / Rsch & Education Grp

Portland, Oregon, 97210, United States

Location

Richmond AIDS Consortium

Richmond, Virginia, 23298, United States

Location

Related Publications (11)

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

  PMID: 11362921 BACKGROUND

• 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)

  BACKGROUND

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

  PMID: 11364573 BACKGROUND

• 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)

  BACKGROUND

• 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)

  BACKGROUND

• 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)

  BACKGROUND

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

  PMID: 11363307 BACKGROUND

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

  PMID: 11362821 BACKGROUND

• 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.

  PMID: 8813040 BACKGROUND

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

  PMID: 11363796 BACKGROUND

• Niu F, Zheng C, Liu L. Exploring causal mechanisms and quantifying direct and indirect effects using a joint modeling approach for recurrent and terminal events. Stat Med. 2023 Sep 30;42(22):4028-4042. doi: 10.1002/sim.9846. Epub 2023 Jul 17.

  PMID: 37461207 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Zidovudine; Zalcitabine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• L Saravolatz

  STUDY CHAIR

• D Winslow

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: December 1, 1995
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (16)