Dideoxycytidine ( Ro 24-2027 ) A Randomized, Open-Label, Comparative Study of Dideoxycytidine ( ddC ) Versus Zidovudine ( AZT ) in Patients With AIDS or Advanced ARC Who Have Received Long-Term AZT Therapy.

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000678

Collaborator

Hoffmann-La Roche (Industry)

320

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

To compare the effectiveness of zalcitabine ( dideoxycytidine; ddC ) therapy to zidovudine ( AZT ) in the treatment of AIDS or advanced AIDS related complex ( ARC ) in patients who have already received at least 1 year of AZT therapy and to define the safety profile.

ddC has been shown to have an antiviral effect, and AZT is known to significantly decrease mortality and to reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. This may be due to the emergence of AZT resistant virus isolated from some patients who have been on long-term AZT therapy. These isolates were still sensitive to ddC. A study of long-term effectiveness of ddC in patients with AIDS or advanced ARC who have been on long-term AZT therapy is warranted because (1) ddC has antiviral activity, (2) there is no blood toxicity associated with taking ddC, and (3) the effectiveness of ddC in test tube studies does not seem to be diminished by decreased effectiveness of AZT.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine Drug: Zalcitabine	Phase 2

Detailed Description

AMENDED: AZT will be administered orally every 4 or 5 hours. Patients in the second arm discontinue AZT and take ddC as two tablets every 8 hours. Duration of the study is 1 year with interim analysis done at 6 months after 75 percent enrollment and at end of the study. Original design: Patients with AIDS or advanced ARC who have been receiving at least 500 mg/day of AZT for at least 48 weeks are randomized to 1 of 2 treatment arms. Patients in the first treatment arm continue their current dose of AZT.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dideoxycytidine ( Ro 24-2027 ) A Randomized, Open-Label, Comparative Study of Dideoxycytidine ( ddC ) Versus Zidovudine ( AZT ) in Patients With AIDS or Advanced ARC Who Have Received Long-Term AZT Therapy.

Actual Primary Completion Date :

Jul 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:

Required:

Aerosolized pentamidine will be given, as tolerated for all patients, for Pneumocystis carinii pneumonia prophylaxis at a dose of 300 mg once every 4 weeks.

Allowed maintenance treatment with:

Pyrimethamine (= or < 75 mg/day).
Sulfadiazine (< 4 gl/day).
Amphotericin (1 mg/kg/day up to 5 days).
Fluconazole (400 mg/day).
Ketoconazole (400 mg/day).
Acyclovir (up to 12.4 mg/kg q8h IV for zoster or up to 4000 mg/day will be allowed PO with precautions - nausea and vomiting possible with doses > 1000 mg/day).
Ganciclovir (6 mg/kg/day).
Medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis, or Mycobacterium avium intracellulare.
Erythropoietin and megace as needed.
Isoniazid if patient has no peripheral neuropathy at study entry and is taking pyridoxine at least 50 mg/day concomitantly.
Phenytoin if patient has no peripheral neuropathy at study entry and has been stable on the drug for at least 3 months.

Patients must have had Pneumocystis carinii pneumonia (PCP) and no other AIDS defining opportunistic infection present when zidovudine (AZT) therapy was first initiated.

Patients must have:

Advanced AIDS related complex (ARC).
Antibody to HIV by federally licensed ELISA and confirmed by Western blot analysis.
Ability to give conformed consent.

Exclusion Criteria

Co-existing Condition:

Patients are excluded who:

Have had zidovudine (AZT) therapy interrupted for > 30 consecutive days at any time during AZT therapy or have been off AZT for > 90 days total.
Have had AZT therapy interrupted for "recurrent" grade 4 toxicity, defined as > one episode of the same grade 4 toxicity after dose interruption or attenuation.
Have visceral or extensive Kaposi's sarcoma requiring therapy or any other malignancy requiring therapy.
Have a history of peripheral neuropathy.

Concurrent Medication:

Excluded:

Other experimental medications, including foscarnet, ribavirin, and fluconazole (prior to IND approval).
Other antiretroviral agents, biologic modifiers or corticosteroids.
Drugs that can cause peripheral neuropathy including phenytoin (under conditions not specifically allowed), hydralazine, metronidazole, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate.

Patients with the following are excluded:

History of peripheral neuropathy or moderate to severe peripheral neuropathy as defined by the combination of signs or symptoms of peripheral neuropathy and findings indicative of peripheral neuropathy on the standardized neurologic exam.
Active opportunistic infection.
Participation in another research treatment study.

Prior Medication:

Excluded:

Dideoxycytidine (ddC).
Didanosine (ddI).

Active substance or alcohol abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Davies Med Ctr	San Francisco	California	United States	94114
2	Mount Zion Med Ctr	San Francisco	California	United States	94115
3	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
4	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
5	Tulane Univ School of Medicine	New Orleans	Louisiana	United States	70112
6	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
7	Albany Med College / AIDS Treatment Ctr	Albany	New York	United States	12203
8	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio	United States	452670405
9	Graduate Hosp	Philadelphia	Pennsylvania	United States	19146
10	N Texas Ctr for AIDS & Clin Rsch	Dallas	Texas	United States	75219