A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00000651
• Collaborator: Hoffmann-La Roche (Industry), Glaxo Wellcome (Industry)
• Enrollment: 750
• Locations: 40
• Patients Per Site: 18.8

Study Details

Study Description

Brief Summary

To evaluate the safety of zalcitabine (dideoxycytidine; ddC) alone and in combination with zidovudine (AZT) versus AZT alone when administered to asymptomatic patients with a CD4 count = or < 200 cells/mm3 and symptomatic patients with a CD4 count = or < 300 cells/mm3. To compare the effectiveness of ddC alone and in combination with AZT versus AZT alone.

ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and 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. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine; Drug: Zalcitabine	Phase 3

Detailed Description

ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and 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. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.

Patients are randomly assigned to 1 of 3 treatment groups. In study arm 1, patients receive AZT plus ddC placebo. In study arm 2, patients receive ddC plus AZT placebo capsules. In study arm 3, patients receive ddC plus AZT. Patients are seen every other week for first 8 weeks and monthly thereafter. Patients are stratified by HIV disease status, length of time receiving AZT, and systemic or local Pneumocystis carinii pneumonia (PCP) prophylaxis. Patients who reach a clinical AIDS-defining endpoint are offered open-label combination therapy.

Study Design

• Study Type: Interventional
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy
• Actual Study Completion Date: May 1, 1993

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

Concurrent Medication:

Required:

• Zidovudine (AZT) = or > 300 mg/day for 6 weeks prior to study entry.

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), candidiasis, and herpes.

• 21 day course of adjuvant systemic corticosteroids for moderate to severe PCP.

• Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, ganciclovir, or 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.

• 14 day course of metronidazole.

• Erythropoietin and megace if clinically indicated.

• Isoniazid if patient has no peripheral neuropathy at entry and is taking pyridoxine = or > 50 mg/day concomitantly.

• Phenytoin if patient has < grade 2 peripheral neuropathy at entry and has been stable on phenytoin = or > 3 months.

Patients must have:

• Ability and willingness to give informed consent.

• Written informed consent from a parent or guardian if < 18 years old.

• Been tolerating zidovudine (AZT) therapy.

• Diagnosis of HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Kaposi's sarcoma or other malignancy requiring therapy.

• Active opportunistic infections.

• Peripheral neuropathy as manifested by complaints of moderate pain, burning, numbness, or tingling in hands/arms or feet/legs; moderate sensory deficit in the upper or lower extremities; or motor weakness in the upper or lower extremities.

Concurrent Medication:

Excluded:

• Other experimental medications.

• Other anti-HIV drugs.

• Biologic response modifiers.

• Cytotoxic chemotherapy.

• Drugs that could cause peripheral neuropathy including phenytoin not specifically allowed, hydralazine, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following are excluded:

• Active opportunistic infection. Must have ended acute therapy at least 14 days prior to study entry.

• Peripheral neuropathy = or > grade 2.

• History of intolerance to 500 to 600 mg/day of zidovudine (AZT) as manifested by the same recurrent grade 3 toxicity requiring dose interruptions and dose reductions to < 500 mg/day or any prior grade 4 toxicity.

• Prior development of peripheral neuropathy on ddI = or > grade 2.

Prior Medication:

Excluded:

• Dideoxycytidine (ddC).

Required:

• Zidovudine (AZT) for total of at least 24 weeks; and included within that time period, AZT = or > 300 mg/day for 6 weeks prior to the study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	UCLA CARE Center CRS	Los Angeles	California	United States	90095
3	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California	United States	92103
4	Ucsd, Avrc Crs	San Diego	California	United States
5	Ucsf Aids Crs	San Francisco	California	United States
6	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
7	University of Colorado Hospital CRS	Aurora	Colorado	United States
8	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
9	Northwestern University CRS	Chicago	Illinois	United States
10	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States
11	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
12	Tulane Hemophilia Treatment Ctr.	New Orleans	Louisiana	United States
13	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana	United States
14	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
15	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
16	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts	United States	02115
17	Bmc Actg Crs	Boston	Massachusetts	United States	02118
18	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
19	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
20	Brigham and Women's Hosp., Div. of Infectious Disease	Boston	Massachusetts	United States
21	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455
22	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States
23	Washington U CRS	Saint Louis	Missouri	United States
24	NJ Med. School CRS	Newark	New Jersey	United States	07103
25	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
26	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States	10016
27	Cornell University A2201	New York	New York	United States	10021
28	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
29	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10029
30	NY Univ. HIV/AIDS CRS	New York	New York	United States
31	Univ. of Rochester ACTG CRS	Rochester	New York	United States
32	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
33	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina	United States
34	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina	United States	27710
35	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina	United States
36	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
37	Case CRS	Cleveland	Ohio	United States	44106
38	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210
39	Pitt CRS	Pittsburgh	Pennsylvania	United States	15213
40	University of Washington AIDS CRS	Seattle	Washington	United States	98122

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Hoffmann-La Roche
• Glaxo Wellcome

Investigators

• Study Chair: M Fischl,
• Study Chair: A Collier,

Study Documents (Full-Text)

None provided.

More Information

Publications

• Blum AS, Dal Pan GJ, Feinberg J, Raines C, Mayjo K, Cornblath DR, McArthur JC. Low-dose zalcitabine-related toxic neuropathy: frequency, natural history, and risk factors. Neurology. 1996 Apr;46(4):999-1003.
• Fichtenbaum CJ, Clifford DB, Powderly WG. Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):169-74.
• Fischl M, Collier A, Stanley K, Ardunio JM, Kazial K, Stein D. The safety and efficacy of zidovudine (ZDV) and zalcitabine (ddC) or ddC alone versus ZDV. ACTG 155 Team of the NIAID. Int Conf AIDS. 1993 Jun 6-11;9(1):68 (abstract no WS-B25-1)
• Fischl MA, Stanley K, Collier AC, Arduino JM, Stein DS, Feinberg JE, Allan JD, Goldsmith JC, Powderly WG. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. Ann Intern Med. 1995 Jan 1;122(1):24-32.
• Johnson VA. Combination therapy: more effective control of HIV type 1? AIDS Res Hum Retroviruses. 1994 Aug;10(8):907-12. Review.
• Keruly J, Kendig N, Feinberg J, Cotton S, Biggs M, Benjamin Y, Francis H, Wade W, Coplin M, Bartlett J. A model for conducting AIDS clinical trials in a state correctional system. Int Conf AIDS. 1992 Jul 19-24;8(2):B236 (abstract no PoB 3873)
• Spino C, Kahn JO, Dolin R, Phair JP. Predictors of survival in HIV-infected persons with 50 or fewer CD4 cells/mm3. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):346-55.
• Zackin RA, Clark RA, Currier JS, Mildvan D. Predictive markers of HIV-related weight loss and determination of differences between populations with weight loss stratified by opportunistic processes. J Acquir Immune Defic Syndr. 1999 Oct 1;22(2):189-93.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000651
• Other Study ID Numbers: ACTG 155; 11130
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Zalcitabine; Antiviral Agents; Zidovudine
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Zidovudine; Zalcitabine

Study Results

No Results Posted as of Nov 2, 2021