A Trial of Alternating 2',3'-Dideoxycytidine and Zidovudine in the Treatment of Patients With Advanced HIV Disease

NCT00000719 | Completed

• 2 other identifiers: ACTG 05011024
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 7

Brief Summary

To determine the long-term safety and tolerance of four alternating and two intermittent regimens of zidovudine ( AZT ) and 2',3'-dideoxycytidine ( zalcitabine; ddC ) in the treatment of patients with advanced HIV disease who have had to discontinue AZT because of true hematologic intolerance to standard reduced doses of AZT. AIDS is a serious infectious disease caused by a new family of retrovirus which is spread primarily through sexual contact and administration of blood or blood products. Individuals who are infected with HIV could therefore benefit from therapy with an effective anti-AIDS virus agent. AZT and ddC have both been tested as antiviral agents and their potentially beneficial effects may be limited by time- and dose-dependent toxicity. A combination regimen using shorter courses of AZT and ddC might therefore be able to sustain treatment without producing toxicity. In addition, since the two drugs exhibit their major toxicity on different organ systems, cumulative or additive toxicity would not be expected.

Conditions

HIV Infections

Keywords

Zalcitabine; Acquired Immunodeficiency Syndrome; 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:
• Allowed:
• Aerosolized pentamidine at prophylactic doses, but its use is discouraged in persons without a history of Pneumocystis carinii pneumonia (PCP).
• Acyclovir for acute disseminated zoster.
• Maintenance doses of pyrimethamine, amphotericin, and pentamidine are allowed for patients who recover from toxoplasmosis, cryptococcosis, or pneumocystosis acquired after study entry.
• Patients included in the study must have HIV infection confirmed by ELISA test and must have a documented history of at least 4 weeks of zidovudine (AZT) treatment.
• While hemoglobin at the start of AZT therapy must have been = or \> 9.5 g/dl and granulocyte count = or \> 1200 cells/mm3 at the start of AZT therapy, hematologic toxicity due to a reduced dose of AZT will be defined as:
• Hematologic toxicity must have occurred during a period when AZT was administered at = or \< 600 mg/day for at least 2 weeks.
• There must have been no evidence of a cause for toxicity other than HIV infection and AZT use.
• Hematologic intolerance may have consisted of hemoglobin toxicity, granulocyte toxicity, or both.
• Recovery from hematologic toxicity must be manifested by the presence of a granulocyte count of \> 1000 cells/mm3 and a hemoglobin of \> 9.5 g/dl. without transfusions during the preceding 4 weeks. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study.
• Prior Medication:
• Required:
• A documented history of at least 4 weeks of zidovudine treatment which resulted in hematologic toxicity at reduced dose.
• Allowed but discouraged:

You may not qualify if:

• Co-existing Condition:
• Patients with the following are excluded:
• Known active AIDS opportunistic infections.
• Known mycobacteremia, although cultures may be pending at the time of enrollment.
• Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months.
• Diabetes.
• Concurrent Medication:
• Excluded:
• Experimental medications.
• Aspirin.
• Acetaminophen.
• Nonsteroidal anti-inflammatory agents should be minimized, with continuous use for \> 72 hours discouraged.
• Chronic suppressive anti-infective therapy other than inhaled pentamidine and neurotoxic drugs should be avoided.
• Continuous therapy for \> 7 days of acyclovir is prohibited except for the acute treatment of disseminated herpes zoster infection.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

USC CRS

Los Angeles, California, 90033, United States

Location

Ucsd, Avrc Crs

San Diego, California, 92103, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Location

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, 70112, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455, 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

• 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. doi: 10.1097/00042560-199510020-00009.

  PMID: 7552481 BACKGROUND

• Bozzette SA, Richman DD. Salvage therapy for zidovudine-intolerant HIV-infected patients with alternating and intermittent regimens of zidovudine and dideoxycytidine. Am J Med. 1990 May 21;88(5B):24S-26S. doi: 10.1016/0002-9343(90)90418-d.

  PMID: 2159706 BACKGROUND

• LeLacheur SF, Simon GL. Exacerbation of dideoxycytidine-induced neuropathy with dideoxyinosine. J Acquir Immune Defic Syndr (1988). 1991;4(5):538-9.

  PMID: 1849990 BACKGROUND

• Bozzette S, Skowron G, Arrezo J, Spector SA, Pettinelli C, Richman DD. ACTG 050: alternating (alt) and intermittent (INT) ddc and AZT in the treatment of persons with advanced HIV infection and hematologic intolerance to AZT. Int Conf AIDS. 1990 Jun 20-23;6(3):192 (abstract no SB425)

  BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

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

• S Bozzette

  STUDY CHAIR

• D Richman

  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: February 1, 1995
• Last Updated: November 3, 2021

Record last verified: 2021-10

Locations

US (7)