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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000969

Collaborator

Bristol-Myers Squibb (Industry), Hoffmann-La Roche (Industry)

400

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zalcitabine Drug: Didanosine	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Sep 1, 1992

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Community Consortium of San Francisco	San Francisco	California	United States	94110
2	Denver CPCRA / Denver Public Hlth	Denver	Colorado	United States	802044507
3	Hill Health Corp	New Haven	Connecticut	United States	06519
4	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware	United States	19899
5	Veterans Administration Med Ctr / Regional AIDS Program	Washington	District of Columbia	United States	20422
6	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
7	AIDS Research Alliance - Chicago	Chicago	Illinois	United States	60657
8	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana	United States	70112
9	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan	United States	48201
10	Henry Ford Hosp	Detroit	Michigan	United States	48202
11	North Jersey Community Research Initiative	Newark	New Jersey	United States	071032842
12	Bronx Lebanon Hosp Ctr	Bronx	New York	United States	10456
13	Clinical Directors Network of Region II	New York	New York	United States	10011
14	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York	United States	10037
15	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon	United States	972109951
16	Richmond AIDS Consortium	Richmond	Virginia	United States	23298