A Comparison of Three Treatments for Advanced HIV Disease in Patients Who Have Received Nucleoside Therapy in the Past

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00001029
• Collaborator: Bristol-Myers Squibb (Industry), Glaxo Wellcome (Industry)
• Enrollment: 654
• Locations: 37
• Patients Per Site: 17.7

Study Details

Study Description

Brief Summary

To compare the efficacy, safety and tolerance, and other clinical and immunologic effects of zidovudine (AZT) plus zalcitabine (dideoxycytidine; ddC), AZT plus didanosine (ddI), and AZT alternating monthly with ddI as measured by differences in survival among HIV-infected persons who have received 6 or more months of nucleoside monotherapy and have a CD4 count greater than or equal to 50 cells/mm3.

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

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

Detailed Description

Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

Patients are randomized to one of three treatment arms: AZT plus ddI, AZT plus ddC, and AZT alone alternating monthly with ddI. Half of the patients receiving AZT alternating monthly with ddI will start with AZT, while the other half will start with ddI. Treatment continues until death or termination of the study. Patients are followed every 4 weeks. The study will include a subset of patients for whom virologic, pharmacokinetic, and macroneurologic assessments will be made.

Study Design

• Study Type: Interventional
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Three-Arm Study Comparing Combination to Monthly Alternating Nucleoside Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3) With a Prior History of Nucleoside 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:

• PCP prophylaxis.

Allowed:

• Erythropoietin.

• Prophylaxis for MAI or fungal infections.

• Antibiotics.

• Over-the-counter, alternative, or regularly prescribed drugs.

• Steroids, if for < 21 days.

Concurrent Treatment:

Allowed:

• Radiation therapy for cutaneous Kaposi's sarcoma.

Patients must have:

• HIV infection.

• CD4 count <= 50 cells/mm3.

• Prior nucleoside monotherapy for at least 6 months.

• Life expectancy of at least 6 months.

Prior Medication: Required:

• Nucleoside monotherapy for at least 6 months. Active alcohol or drug abuse.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Severe peripheral neuropathy.

• Psychological or emotional problems sufficient to prevent study compliance.

Concurrent Medication:

Excluded:

• Systemic chemotherapy for malignancy.

• Acute or induction therapy for opportunistic infection.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.

• Grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.

Prior Medication:

Excluded:

• Non-study nucleosides or biologic response modifiers within 7 days prior to study entry.

• Acute therapy for opportunistic process within 14 days prior to study entry.

• Acute systemic therapy for other medical conditions within 14 days prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	Stanford CRS	Palo Alto	California	United States	94115
3	Ucsd, Avrc Crs	San Diego	California	United States	92103
4	Ucsf Aids Crs	San Francisco	California	United States
5	Santa Clara Valley Med. Ctr.	San Jose	California	United States
6	San Mateo County AIDS Program	San Mateo	California	United States
7	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
8	University of Colorado Hospital CRS	Aurora	Colorado	United States
9	Univ. of Miami AIDS CRS	Miami	Florida	United States
10	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
11	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
12	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
13	Northwestern University CRS	Chicago	Illinois	United States
14	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
15	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
16	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa	United States
17	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
18	Bmc Actg Crs	Boston	Massachusetts	United States	02118
19	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States
20	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota	United States	55415
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	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska	United States	68198
25	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10003
26	NY Univ. HIV/AIDS CRS	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	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
30	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
31	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
32	Case CRS	Cleveland	Ohio	United States	44106
33	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States
34	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
35	University of Washington AIDS CRS	Seattle	Washington	United States	98122
36	Puerto Rico-AIDS CRS	San Juan		Puerto Rico	00936
37	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya		Tanzania

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Bristol-Myers Squibb
• Glaxo Wellcome

Investigators

• Study Chair: WK Henry,
• Study Chair: JO Kahn,
• Study Chair: HH Balfour,

Study Documents (Full-Text)

None provided.

More Information

Publications

• Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. Review.
• Henry K, Erice A, Tierney C, Balfour HH Jr, Fischl MA, Kmack A, Liou SH, Kenton A, Hirsch MS, Phair J, Martinez A, Kahn JO. A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS. AIDS Clinical Trial Group 193A Study Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Dec 1;19(4):339-49.
• Henry K, Tierney C, Kahn J, Balfour H, Jiang Q, Kmack A, Fischl M. A randomized, double-blind, placebo-controlled study comparing combination nucleoside and triple therapy for the treatment of advanced HIV disease (CD4 less than or equal to 50/mm(3)). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:207 (abstract no LB6)

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00001029
• Other Study ID Numbers: ACTG 193; 11168
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 4, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Zalcitabine; Didanosine; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; Zidovudine
• Additional relevant MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Zidovudine; Didanosine; Zalcitabine

Study Results

No Results Posted as of Nov 4, 2021