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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000719
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention
HIV Infections
Drug: Zidovudine
Drug: Zalcitabine

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Alternating 2',3'-Dideoxycytidine and Zidovudine in the Treatment of Patients With Advanced HIV Disease

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 96
Study Completion Date: February 1995
Detailed Description:

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.

There are six study regimens. Four of these are alternating regimens: A 2-week cycle consisting of 1 week of AZT followed by 1 week of ddC and an 8-week cycle consisting of 4 weeks of AZT followed by 4 weeks of ddC. All patients on alternating regimens will receive AZT alone at the standard dose orally every 4 hours for either 1 or 4 weeks. After the AZT is stopped, patients receive ddC orally every 4 hours for either 1 or 4 weeks, which completes a treatment cycle. One of two doses of ddC is studied in each alternating regimen. Both doses must be tested because the optimal dose cannot be inferred from tests that have already been done. AZT is administered first in the hope that AZT-mediated reduction of p24 antigen load may reduce the occurrence of acute ddC toxicity. Two intermittent regimens are also studied and are included to assess the contribution of each drug in the alternating regimens. One program consists of 1 week of AZT followed by 1 week of no drug. The other consists of 1 week of ddC followed by 1 week of no drug. Drug dosing continues for a total of 48 weeks unless toxicity develops. Patients who complete 48 weeks of therapy are followed for 4 additional weeks off therapy. Patients removed from study because of toxicity are followed for 4 weeks or until toxicity resolves. If study participants complete 48 weeks of therapy and meet criteria for efficacy, the study drug regimen may be continued for an additional 32 weeks. A 4 week wash-out period off drug will not be required for patients continuing on study. AMENDED 09/24/90 Drug dosing will be discontinued as of 11/30/90.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

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:
  • A1-721.

Exclusion Criteria

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.

Patients with the following are excluded:

  • 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.
  • Known active AIDS opportunistic infections. 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:

Excluded within 30 days of study entry:

  • Any antiretroviral agents except zidovudine (AZT).
  • Discouraged:
  • A1-721.
  • Pentamidine at prophylactic doses in persons without a history of Pneumocystis carinii pneumonia (PCP).

Active substance and/or alcohol abuse.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000719

Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033
Ucsd, Avrc Crs
San Diego, California, United States, 92103
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
United States, Louisiana
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States, 70112
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Investigators
Study Chair: S Bozzette
Study Chair: D Richman
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000719     History of Changes
Other Study ID Numbers: ACTG 050, 11024
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Acquired Immunodeficiency Syndrome
Zidovudine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zalcitabine
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 16, 2014