A Clinical Trial of Alternating and Intermittent Regimens of 2',3'-Dideoxycytidine and 3'-Azido-3'-Deoxythymidine in the Treatment of Patients With AIDS and Advanced ARC

NCT00000718 | Completed

• 2 other identifiers: ACTG 04711021
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if alternating zidovudine (AZT) and zalcitabine (dideoxycytidine; ddC) (first one and then the other) or intermittent therapy (1 week of drug then 1 week off) will lessen the toxic effects of either drug alone, while still inhibiting HIV (the AIDS virus) in patients with AIDS or AIDS related complex. AZT extends the survival of some patients with AIDS, and both AZT and ddC are known to inhibit the growth of HIV. When AZT or ddC is given continuously over a prolonged period of time, toxic effects occur that are not found when the drugs are given for 4 - 6 weeks. It is hoped that by alternating the drugs or by giving one drug intermittently, the toxic effects can be decreased without lowering the therapeutic effectiveness of the drugs.

Conditions

HIV Infections

Keywords

Zalcitabine; Dose-Response Relationship, Drug; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Zidovudine

Interventions

Zidovudine DRUG

Zalcitabine DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Encouraged though not required:
• Inhaled pentamidine as prophylaxis for Pneumocystis carinii pneumonia (PCP).
• Allowed:
• AL-721 use is discouraged but not prohibited.
• Use of aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents should be minimized, with continuous use for \> 72 hours discouraged.
• Acute therapy (7 days) with oral acyclovir.
• Acute therapy with ketoconazole.
• Concurrent Treatment:
• Allowed:
• Up to 4 units of packed red blood cells for hemoglobin toxicity.
• All patients must have the following:
• A consistently positive serum HIV p24 antigen = or \> 70 pg/ml, defined by the Abbott HIV antigen test, on two occasions. The tests must be within 1 month of study entry, separated by at least 72 hours, and the last must be within 2 weeks of starting therapy. Any negative antigen test during the period will exclude the patient from the study.
• A positive antibody to HIV confirmed by any federally licensed ELISA test kit.
• Patients in group A must have AIDS related complex (ARC) as defined by the documented presence of at least one of the following:

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• Transfusion dependence requiring 2 units of blood more than once per month.
• Significant malabsorption (\> 10 percent weight loss within the past 3 months with serum carotene \< 75 IU/ml or vitamin A \< 74 IU/ml).
• Significant cardiac or liver disease.
• Significant neurologic abnormalities defined by any one of the following:
• A significant abnormality on the ddC Neuropathy Targeted Symptom Questionnaire defined as a symptom score \> 4 (moderate severity) in any one of six categories or a score \> 2 (mild severity) in any two of six categories.
• Moderate abnormalities on standardized neurologic exam.
• Any severe abnormality (a value = or \> 4.0) on standardized 4-arm quantitative sensory testing of vibration threshold.
• Diabetes, renal failure, or alcoholism.
• Dose-limiting or transfusion-requiring toxicity during a previous course of zidovudine therapy.
• History of idiopathic thrombocytopenic purpura.
• Requirement for prolonged acyclovir therapy. Patients in group A must not have the following:
• Opportunistic infection or malignancy fulfilling the CDC definition of AIDS.
• Neoplasms other than basal cell carcinoma of the skin or in situ carcinoma of the cervix. Patients in group B must not have the following:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Related Publications (6)

• Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. doi: 10.1128/jcm.35.3.631-635.1997.

  PMID: 9041402 BACKGROUND

• Gries JM, Troconiz IF, Verotta D, Jacobson M, Sheiner LB. A pooled analysis of CD4 response to zidovudine and zalcitabine treatment in patients with AIDS and AIDS-related complex. Clin Pharmacol Ther. 1997 Jan;61(1):70-82. doi: 10.1016/S0009-9236(97)90183-1.

  PMID: 9024175 BACKGROUND

• Merigan TC. Treatment of AIDS with combinations of antiretroviral agents. Am J Med. 1991 Apr 10;90(4A):8S-17S. doi: 10.1016/0002-9343(91)90405-m.

  PMID: 1850192 BACKGROUND

• Skowron G, Merigan TC. Alternating and intermittent regimens of zidovudine (3'-azido-3'-deoxythymidine) and dideoxycytidine (2',3'-dideoxycytidine) in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Am J Med. 1990 May 21;88(5B):20S-23S. doi: 10.1016/0002-9343(90)90417-c.

  PMID: 2159705 BACKGROUND

• Skowron G, Bozzette SA, Lim L, Pettinelli CB, Schaumburg HH, Arezzo J, Fischl MA, Powderly WG, Gocke DJ, Richman DD, Pottage JC, Antoniskis D, McKinley GF, Hyslop NE, Ray G, Simon G, Reed N, LoFaro ML, Uttamchandani RB, Gelb LD, Sperber SJ, Murphy RL, Leedom JM, Grieco MH, Zachary J, Hirsch MS, Spector SA, Bigley J, Soo W, Merigan TC. Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. Ann Intern Med. 1993 Mar 1;118(5):321-30. doi: 10.7326/0003-4819-118-5-199303010-00001.

  PMID: 8094279 BACKGROUND

• Fitzgibbon JE, Howell RM, Schwartzer TA, Gocke DJ, Dubin DT. In vivo prevalence of azidothymidine (AZT) resistance mutations in an AIDS patient before and after AZT therapy. AIDS Res Hum Retroviruses. 1991 Mar;7(3):265-9. doi: 10.1089/aid.1991.7.265.

  PMID: 2064825 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Zidovudine; Zalcitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine

Study Officials

• G Skowron

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: September 1, 1991
• Last Updated: November 3, 2021

Record last verified: 2021-10

Locations

US (1)