Double-Blind Comparison of the Efficacy of Continued Zidovudine Versus 2',3'-Dideoxyinosine (ddI) (BMY-40900) for the Treatment of Patients With AIDS or AIDS-Related Complex and Increasing Symptomatology Despite Treatment With Zidovudine

To compare the efficacy and safety of orally administered didanosine (ddI) with orally administered zidovudine (AZT) in the treatment of patients who exhibit increasing clinical deterioration despite treatment with AZT.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Didanosine

• Study Type: Interventional
• Enrollment: 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 009275800
    • UPR School of Medicine
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Univ of Arizona / Health Science Ctr
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Univ Med School
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • G E Morey Jr
    • Orlando, Florida, United States, 32806
      • VP Med Services / HHCS Research Institute Inc
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
  • Illinois
    • Hines, Illinois, United States, 60141
      • Edward Hines Veterans Administration Hosp
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Univ of Kansas School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper Hosp
  • New York
    • Albany, New York, United States, 12203
      • Albany Med College / AIDS Treatment Ctr
  • Ohio
    • Toledo, Ohio, United States, 43699
      • Med College of Ohio
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ of Pennsylvania / HIV Clinic
  • Texas
    • Dallas, Texas, United States, 75235
      • Univ of Texas Southwestern Med Ctr of Dallas
    • Galveston, Texas, United States, 775550882
      • Univ TX Galveston Med Branch
    • San Antonio, Texas, United States, 78284
      • Audie L Murphy Veterans Administration Hosp
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Univ of Utah School of Medicine
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Dr Stephen L Green
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Milwaukee County Med Complex

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed for Hematologic toxicity:

• Erythropoietin.
• Colony-Stimulating Factors.
• Allowed for prophylaxis of Pneumocystis carinii pneumonia (PCP):
• Aerosolized pentamidine.
• Trimethoprim/sulfamethoxazole.
• Dapsone.
• NOTE:
• If intravenous pentamidine is required for treatment of PCP, study drug should be suspended until one week after completion of intravenous pentamidine.
• Allowed:
• Prophylactic or suppressive therapy begun prior to study entry with the exception of neurotoxic agents (as defined in the protocol).

Concurrent Treatment:

Allowed:

• Transfusions for hematologic toxicity.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Active acute AIDS defining infection.
• Clinical evidence of acute pancreatitis in the last two years or chronic pancreatitis.
• Dementia of such severity that patient cannot give informed consent.
• Grade 2 or worse peripheral neuropathy as defined by Targeted Neuropathy Score (Schaumberg).
• Prior Cytomegalovirus disease requiring ongoing systemic ganciclovir therapy.
• Extensive Kaposi's sarcoma or other malignancy requiring systemic cytotoxic myelosuppressive or neurotoxic chemotherapy.
• Cardiomyopathy or the need for antiarrhythmic therapy.
• Inability to tolerate at least 600 mg per day of zidovudine (AZT).
• Seizures within the last 6 months or the need for anticonvulsant therapy.

Concurrent Medication:

Excluded:

• Ganciclovir (DHPG).
• Myelosuppressive or neurotoxic chemotherapy.
• Antiarrhythmic therapy.
• Anticonvulsant therapy.
• Neurotoxic agents (as defined in the protocol).
• NOTE:
• If intravenous pentamidine is required for treatment of Pneumocystis carinii pneumonia (PCP), study drug should be suspended until 1 week after completion of intravenous pentamidine.

Patients with the following are excluded:

• Symptoms and conditions defined in the Patient Exclusion Co-Existing Conditions field.
• Average of two sequential CD4 counts from SciCor Clinical Laboratories in the 30 days prior to study entry > 300 cells/mm3.

Prior Medication:

Excluded, participation in studies using:

• Dideoxyinosine (ddI).
• 2',3'-Dideoxy-2',3'-didehydrothymidine (d4T).
• Dideoxycytidine (ddC).
• Excluded within one month of study entry:
• Any other experimental antiretroviral compounds.

Patients must:

• Have documented HIV positivity via ELISA.
• Meet CDC criteria for AIDS or AIDS related complex (ARC).
• Have received zidovudine (AZT) for = or > 6 months and tolerated a dose of at least 500 mg per day without significant hematologic toxicity.
• Have no acute AIDS defining opportunistic infection, but may be receiving suppressive therapy for such infections.
• Demonstrate at least one of the following criteria for clinical deterioration despite AZT therapy within 4 weeks prior to study entry (8 weeks prior for weight loss):
• involuntary weight loss of more than 5 percent of the body weight occurring over the 8 week period prior to study entry, Karnofsky score = or > 50 but demonstrating a fall = or > 20 from previous level of functioning (assessment must be persistent on two occasions at least 14 days apart), unexplained fever of = or > 38 degrees C (despite evaluation defined in protocol) for more than 7 days, appearance of newly diagnosed oral hairy leukoplakia or oral candidiasis, or recurrence of a previously quiescent multidermatomal varicella-zoster, appearance of dermatologic afflictions (e.g. psoriasis, molluscum contagiosum, or newly diagnosed seborrheic dermatitis), appearance of chronic herpetic ulcers not responsive to acyclovir therapy.

Required:

• Zidovudine (AZT) for = or > 6 months prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Ruedy N, et al. Results of long term follow-up of a double blind study of ddI vs continued AZT among individuals with CD4s 200-500/mm3. Int Conf AIDS. 1994 Aug 7-12;10(2):16 (abstract no 358B)

Study record dates

Study Major Dates

• Study Completion (Actual): April 1, 1992

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): August 5, 2011
• Last Update Submitted That Met QC Criteria: August 4, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Didanosine; Zidovudine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; AIDS-Related Complex; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine; Didanosine
• Other Study ID Numbers: 039B; AI454-010