A Prospective, Randomized, Open-Label, Comparative Trial of Dideoxyinosine (ddI) Versus Dideoxycytidine (ddC) in HIV-Infected Patients Who Are Intolerant of or Who Have Failed Zidovudine (AZT) Therapy

NCT00000969 | Completed

• 2 other identifiers: CPCRA 00211554
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 16

Brief Summary

To evaluate and compare the effectiveness and toxicity associated with didanosine ( ddI ) and zalcitabine ( dideoxycytidine; ddC ) in patients with HIV infection who are intolerant of or have failed zidovudine ( AZT ) therapy. Alternative and less toxic treatments need to be investigated for the treatment of HIV infection. Studies have shown that the dideoxynucleosides ddI and ddC may be effective antiretroviral agents in the treatment of HIV-infected individuals. However, ddI and ddC have yet to be compared on the basis of patient survival, drug tolerance, immunologic and virologic effectiveness, and the incidence of opportunistic infection or opportunistic malignancy. Results of this study will yield information regarding the relative therapeutic benefits and toxicities of each drug while providing alternative treatment to patients who are unable to tolerate or have had progression of disease while on AZT.

Conditions

HIV Infections

Keywords

Zalcitabine; Didanosine; Drug Evaluation; Zidovudine

Interventions

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:

• Concurrent Medication:
• Allowed:
• Acyclovir (if patient is also receiving ddC, clinical monitoring should be more frequent).
• Analgesics, antiemetics, antidiarrheal agents, or other necessary treatment for symptomatic therapy.
• Interferons for maintenance therapy of Kaposi's sarcoma.
• GM-CSF.
• Required:
• Prophylaxis against Pneumocystis carinii pneumonia (PCP) if their absolute CD4+ lymphocyte count is \< 200 cells/mm3 at study entry. PCP prophylaxis for patient with CD4+ counts between 200 and 300 cells/mm3 is at discretion of patient's primary physician.
• NOTE: There is potential interaction of ddI and dapsone.
• Concurrent Treatment:
• Allowed:
• Transfusion, erythropoietin.
• Patients must have the following:
• Zidovudine (AZT) failure after having received a cumulative duration of at least 6 months.
• AZT intolerance - rechallenge is not required for patients exhibiting = or \> grade III cutaneous symptoms.

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• Any disorders for which the study drugs are contraindicated (didanosine (ddI)) is contraindicated in renal impairment, heart disease, receiving renal dialysis.
• Active opportunistic infection.
• Concurrent Medication:
• Excluded:
• Other antiretroviral agents.
• Use of drugs associated with peripheral neuropathy or use of agents that may cause pancreatitis including intravenous pentamidine and alcohol should be restricted or avoided.
• Concurrent Treatment:
• Excluded:
• Other concurrent antiretroviral clinical trials.
• Patients with the following are excluded:
• History of pancreatitis, peripheral neuropathy, uncontrolled seizures, renal impairment, heart disease, stage 2 or higher ADC.
• Any other disorders for which the study drugs are contraindicated, i.e., ddI is contraindicated in renal impairment, patients receiving renal dialysis, and heart disease.
• Receiving acute therapy for active AIDS defining opportunistic infection on enrollment.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (16)

Community Consortium of San Francisco

San Francisco, California, 94110, United States

Location

Denver CPCRA / Denver Public Hlth

Denver, Colorado, 802044507, 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, 071032842, 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

Bronx Lebanon Hosp Ctr

The Bronx, New York, 10456, United States

Location

Portland Veterans Adm Med Ctr / Rsch & Education Grp

Portland, Oregon, 972109951, United States

Location

Richmond AIDS Consortium

Richmond, Virginia, 23298, United States

Location

Related Publications (7)

• Bjorling LE, Hodges JS. Rule-based ranking schemes for antiretroviral trials. Stat Med. 1997 May 30;16(10):1175-91. doi: 10.1002/(sici)1097-0258(19970530)16:103.0.co;2-g.

  PMID: 9179982 BACKGROUND

• Hogan CH, Hodges JS, Mugglin A, Peterson PM, Abrams DI, Saravolatz L. The perils of visit-driven endpoints in antiretroviral trials. Int Conf AIDS. 1996 Jul 7-12;11(1):237 (abstract no TuB522)

  BACKGROUND

• Fleming TR, Neaton JD, Goldman A, DeMets DL, Launer C, Korvick J, Abrams D. Insights from monitoring the CPCRA didanosine/zalcitabine trial. Terry Beirn Community Programs for Clinical Research on AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 2:S9-18.

  PMID: 7552519 BACKGROUND

• Goldman AI, Carlin BP, Crane LR, Launer C, Korvick JA, Deyton L, Abrams DI. Response of CD4 lymphocytes and clinical consequences of treatment using ddI or ddC in patients with advanced HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Feb 1;11(2):161-9. doi: 10.1097/00042560-199602010-00007.

  PMID: 8556398 BACKGROUND

• Abrams D, Goldman A, Launer C, Korvick J, Crane L, Deyton L. Results of a randomized open-label comparison trial of ddI and ddC in HIV infected patients who are intolerant of or have failed ZDV therapy; CPCRA 002. The Terry Beirn Community Programs for Clinical Research on AIDS. Int Conf AIDS. 1993 Jun 6-11;9(1):67 (abstract no WS-B24-4)

  BACKGROUND

• Abrams DI, Goldman AI, Launer C, Korvick JA, Neaton JD, Crane LR, Grodesky M, Wakefield S, Muth K, Kornegay S, et al. A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. The Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. 1994 Mar 10;330(10):657-62. doi: 10.1056/NEJM199403103301001.

  PMID: 7906384 BACKGROUND

• Soeiro-de-Souza MG, Bio DS, David DP, Rodrigues dos Santos D Jr, Kerr DS, Gattaz WF, Machado-Vieira R, Moreno RA. COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes. J Affect Disord. 2012 Feb;136(3):370-6. doi: 10.1016/j.jad.2011.11.021. Epub 2012 Jan 4.

  PMID: 22222175 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kaplan C

  STUDY CHAIR

• Crane L

  STUDY CHAIR

• Abrams D

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: September 1, 1992
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (16)