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

• Status: Completed
• Trial end date: 1992-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Hoffmann-La Roche
• Treatments: Didanosine; Zalcitabine; Zidovudine

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.