(Ro 24-2027) A Randomized, Double-Blind, Comparative Study of Dideoxycytidine (ddC) Versus Zidovudine (AZT) in Patients With AIDS or Advanced ARC

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00000679

Collaborator

Hoffmann-La Roche (Industry)

600

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

To show that zalcitabine (dideoxycytidine; ddC) is at least as effective as zidovudine (AZT) in the treatment of AIDS or advanced AIDS related complex (ARC), and also that ddC shows a different safety profile than AZT.

In clinical studies, ddC shows antiviral activity. Because of the antiviral activity, and because of the low incidence of mild, reversible neurotoxicity and absence of blood-related toxicity with low dose ddC therapy, a long-term Phase II/III study comparing ddC to AZT in patients with AIDS or advanced ARC is now warranted.

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

Detailed Description

After screening, physical examination and laboratory tests (within 14 days of entry) patients are randomized to one of two treatment groups. They receive either ddC plus an AZT placebo or AZT plus a ddC placebo. Because it is a blinded study, patients do not know which group they are in. Patients are evaluated weekly for the first 10 weeks and then biweekly thereafter.

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Treatment

Official Title:

(Ro 24-2027) A Randomized, Double-Blind, Comparative Study of Dideoxycytidine (ddC) Versus Zidovudine (AZT) in Patients With AIDS or Advanced ARC

Actual Primary Completion Date :

Feb 1, 1994

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

Allowed:

Aerosolized pentamidine (300 mg once every 4 weeks) for Pneumocystis carinii pneumonia (PCP) prophylaxis.
Neuroleptics, benzodiazepines, or antidepressants if patient has been stable with chronic treatment > 1 month.
Low dose benzodiazepines or low dose antidepressants.
Drugs that are unlikely to cause increased toxicity with either study drug and are unlikely to cause peripheral neuropathy.
Drugs with little nephrotoxicity, hepatotoxicity, or cytotoxicity that the patient has been taking and tolerating well.
Acyclovir (up to 600 mg/kg/day) for up to 21 days.
Ketoconazole (up to 400 mg/day) Nystatin.
Low-dose acetaminophen or nonsteroidal anti-inflammatory agents.
Isoniazid if patient has no evidence of peripheral neuropathy at entry and if patient takes 50 mg/day pyridoxine concomitantly with isoniazid.
Allowed with interruption of study medication for up to 21 days per episode and for a total of 42 days for the study:
Drugs that could cause serious additive toxicity when coadministered with either study medication for treatment of an acute intercurrent illness or opportunistic infection, including:
Acyclovir (< 600 mg/day), fluconazole, systemic pentamidine, foscarnet, pyrimethamine, triple sulfa, ansamycin, ganciclovir, trimethoprim / sulfamethoxazole.

Patients must have a diagnosis of AIDS or advanced AIDS related complex (ARC). At least 20 percent of the patients must have a consistently positive serum HIV p24 antigen (= or > 70 pg/ml) as defined by the Abbott HIV antigen test, on two separate occasions at least 72 hours apart.

Patients found at screening to have a temperature > 38.5 degrees C should be evaluated for the possibility of an occult opportunistic or bacterial infection or neoplasm. If this complete evaluation reveals an infection, they can be entered. If this evaluation is unrevealing, they may be entered after evaluation is completed but while mycobacterial cultures are still pending. Patients with a history of unexplained temperatures > 38.5 degrees C should be evaluated as above and/or be afebrile (temperature < 38.0 degrees C) for 2 weeks prior to study entry.
Allowed: Kaposi's sarcoma not specifically excluded, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
Current positive venereal disease research label (VDRL) and fluorescent treponemal antibody (FTA) if treated as for asymptomatic neurosyphilis.

Prior Medication:

Allowed:

Drugs that cause peripheral neuropathy and drugs that could cause significant increased toxicity with zidovudine (AZT) or dideoxycytidine (ddC) including experimental drugs if therapy with these drugs is completed and patient is stable for 14 days.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

Active AIDS defining opportunistic infection or other active intercurrent illness is excluded if ongoing treatment requires the use of excluded concomitant medication.
Patients with symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study, or with current neoplasms not specifically allowed.
Severe AIDS dementia complex defined by a score of < 23 on the Mini-Mental State Exam.
Signs, symptoms, or history of peripheral neuropathy.
Significant cardiac disease, defined as history of ventricular arrhythmias requiring medication, prior myocardial infarct, or history of angina or ischemia changes on ECG (electrocardiography).
Requiring > 2 weeks of acyclovir therapy at > 600 mg/day.
Current positive venereal disease research label (VDRL) and fluorescent treponemal antibody (FTA) not specifically allowed.
Significant liver disease.

Concurrent Medication:

Excluded:

Drugs that cause peripheral neuropathy:
chloramphenicol, cisplatinum, iodoquinol, dapsone, phenytoin, disulfiram, ethionamide, glutethimide, gold, hydralazine, ribavirin, metronidazole, vincristine, nitrofurantoin.
Drugs that could cause significant increased toxicity with zidovudine (AZT) or dideoxycytidine (ddC), including experimental drugs not specifically allowed.
Drugs that could cause seizures or changes in mental status or neurological examination.

Concurrent Treatment:

Excluded:

Transfusion dependency.

Patients with the following are excluded:

Active AIDS defining opportunistic infection or other active intercurrent illness if ongoing treatment requires use of excluded concomitant medication.
Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry, or current neoplasms not specifically allowed.
Severe AIDS dementia complex defined by a score of < 23 on the Mini-Mental State Exam.
Signs, symptoms, or history of peripheral neuropathy.
Unwilling or unable to sign informed consent.

Prior Medication:

Excluded:

Zidovudine (AZT), dideoxycytidine (ddC), or any other antiretroviral nucleoside analog.
Excluded within 90 days of study entry:
Any experimental drug including fluconazole, ganciclovir, foscarnet, erythropoietin, or ribavirin.

Excluded within 90 days of study entry:

Drugs that have caused significant nephrotoxicity or significant hepatotoxicity.
Drugs that could cause peripheral neuropathy including phenytoin, hydralazine, metronidazole, and nitrofurantoin.
Systemic corticosteroids or immunomodulators including interferon and interleukin.

Prior Treatment:

Excluded within 30 days of study entry:

Radiation therapy.

Active substance or alcohol abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Foundation Hosp	Harbor City	California	United States	90710
2	Kaiser Permanente Med Ctr	Los Angeles	California	United States	90027
3	UCD Med Ctr	Sacramento	California	United States	95817
4	Davies Med Ctr	San Francisco	California	United States	94114
5	Mount Zion Med Ctr	San Francisco	California	United States	94115
6	San Francisco Veterans Administration Med Ctr	San Francisco	California	United States	94121
7	Santa Clara Valley Med Ctr	San Jose	California	United States	95128
8	Georgetown Univ Med Ctr	Washington	District of Columbia	United States	20007
9	Ctr for Special Immunology	Fort Lauderdale	Florida	United States	33308
10	Comprehensive Clinic / Dr Robert Schwartz	Fort Myers	Florida	United States	33901
11	Med Service	Miami	Florida	United States	33125
12	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
13	Northwestern Univ Med School	Chicago	Illinois	United States	60611
14	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
15	New England Med Ctr	Boston	Massachusetts	United States	02111
16	Henry Ford Hosp	Detroit	Michigan	United States	48202
17	Saint Michael's Med Ctr	Newark	New Jersey	United States	07102
18	Albany Med College / AIDS Treatment Ctr	Albany	New York	United States	12203
19	Sunset Park Health Ctr - Lutheran Med Ctr	Brooklyn	New York	United States	11220
20	Bowman Gray School of Medicine / North Carolina Baptist Hosp	Winston-Salem	North Carolina	United States	27103
21	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio	United States	44106
22	Graduate Hosp	Philadelphia	Pennsylvania	United States	19146
23	N Texas Ctr for AIDS & Clin Rsch	Dallas	Texas	United States	75219
24	Univ TX Galveston Med Branch	Galveston	Texas	United States	77550
25	Baylor College of Medicine	Houston	Texas	United States	77030