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

Condition(s) targeted: HIV Infections

Intervention: Zalcitabine (Drug); Didanosine (Drug)

Phase: N/A

Status: Active, not recruiting

Sponsored by: Bristol-Myers Squibb

Official(s) and/or principal investigator(s):
Kaplan C, Study Chair
Crane L, Study Chair
Abrams D, Study Chair

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.

Official title: 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

Study design: Treatment, Parallel Assignment

Detailed description: 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.

After baseline screening, patients are randomized to one of two treatment arms (ddI or ddC). Subjects are evaluated biweekly for the first 4 weeks of study, at 2 months, and every other month thereafter. Three dose levels of ddI (based on patient's weight at study entry) are compared with two dose levels of ddC (also based on patient weight). Patients who reach a new progression-of-disease primary endpoint after at least 12 weeks of treatment or a drug intolerance endpoint have the option of switching over to the alternate study drug; however, participants are encouraged to remain on their original drug assignment whenever possible. For any switchover, patients must be off the originally assigned drug for at least 72 hours before switching. Only one switchover is allowed.

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

Criteria:

Inclusion Criteria

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.

- Diagnosis of AIDS or CD4+ = or < 300 cells/mm3 OR AIDS-defining illness other than

Kaposi's sarcoma.

- Willingness and ability to comply with protocol.

- Informed consent must be obtained for all study participants in accordance with state

law, local IRB requirements, and 45 CFR Part 46. AMENDED 11/19/90 to include assent by minors if they are physically able, in addition to consent by parents.

Exclusion Criteria

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.

Prior Medication:

Excluded:

- Didanosine (ddI).

- Dideoxycytidine (ddC) .

Excessive alcohol use that, in investigator's opinion, puts patient at risk of developing pancreatic disease.

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

Denver CPCRA / Denver Public Hlth, Denver, Colorado 802044507, 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

Henry Ford Hosp, Detroit, Michigan 48202, United States

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

North Jersey Community Research Initiative, Newark, New Jersey 071032842, United States

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

Bronx Lebanon Hosp Ctr, Bronx, New York 10456, United States

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

Portland Veterans Adm Med Ctr / Rsch & Education Grp, Portland, Oregon 972109951, United States

Richmond AIDS Consortium, Richmond, Virginia 23298, United States

Click here for more information about Zalcitabine

Click here for more information about Didanosine

Related publications:

Bjorling LE, Hodges JS. Rule-based ranking schemes for antiretroviral trials. Stat Med. 1997 May 30;16(10):1175-91.

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)

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.

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.

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)

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.

Last updated: June 23, 2005