A Phase II Efficacy Study Comparing 2',3'-Dideoxyinosine (ddI) (BMY-40900) and Zidovudine Therapy of Patients With HIV Infection Who Have Been on Long Term Zidovudine Treatment

March 11, 2011 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To compare the effectiveness and toxicity of didanosine (ddI) and zidovudine (AZT) in patients with AIDS or advanced AIDS-related complex (ARC) who have tolerated AZT therapy for 12 months or longer. Per amendment, asymptomatic patients with CD4 counts less than 200 cells/mm3 are eligible.

AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication of HIV with less apparent toxicity than AZT. Studies indicate that ddI remains active in the body for at least 12 hours; thus benefits of ddI might be achieved with a low frequency of drug administration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AZT is effective in reducing mortality in patients with AIDS who receive the drug after the first episode of Pneumocystis carinii pneumonia (PCP) and in patients with advanced ARC. However, AZT therapy has been associated with significant toxicities. In addition, the effectiveness of AZT appears to decrease during the second and third years of therapy. For these reasons, the development of alternative therapy that would be at least as effective but less toxic is of great importance. The drug ddI is an antiviral agent that inhibits replication of HIV with less apparent toxicity than AZT. Studies indicate that ddI remains active in the body for at least 12 hours; thus benefits of ddI might be achieved with a low frequency of drug administration.

Two dose levels of ddI, each adjusted depending on patient's weight at study entry, are compared with a variable dosage regimen of AZT (the dose which the patient is tolerating at the time of study entry). Randomization is stratified by baseline CD4 cell count (less than 100 or 100-300) and Medical Center. This study continues for at least 12 months after the entry of the first subject. Patients randomized to AZT will receive orally. All patients randomized to AZT also receive a ddI placebo at 12 hour intervals. Patients randomized to ddI receive AZT placebo.

Study Type

Interventional

Enrollment

750

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 009275800
        • San Juan Veterans Administration Med Ctr
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Ctr
      • Los Angeles, California, United States, 900276016
        • Children's Hosp of Los Angeles/UCLA Med Ctr
      • Los Angeles, California, United States, 90033
        • Los Angeles County - USC Med Ctr
      • Los Angeles, California, United States, 900481804
        • Cedars Sinai / UCLA Med Ctr
      • Los Angeles, California, United States, 905022004
        • Harbor - UCLA Med Ctr / UCLA School of Medicine
      • Palo Alto, California, United States, 94304
        • Palo Alto Veterans Adm Med Ctr / Stanford Univ
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco AIDS Clinic / San Francisco Gen Hosp
      • San Francisco, California, United States, 94115
        • Stanford at Kaiser / Kaiser Permanente Med Ctr
      • Stanford, California, United States, 94305
        • Stanford Univ School of Medicine
      • Sylmar, California, United States, 91342
        • Olive View Med Ctr
      • Sylmar, California, United States, 91342
        • Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr
      • Torrance, California, United States, 90502
        • Harbor UCLA Med Ctr
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
      • Denver, Colorado, United States, 80262
        • Mountain States Regional Hemophilia Ctr / Univ of Colorado
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • George Washington Univ Med Ctr
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • G E Morey Jr
      • Miami, Florida, United States, 331361013
        • Univ of Miami School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
      • Hines, Illinois, United States, 60141
        • Edward Hines Veterans Administration Hosp
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Univ of Kansas School of Medicine
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Louisiana Comprehensive Hemophilia Care Ctr
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State Univ Med Ctr / Tulane Med School
      • New Orleans, Louisiana, United States, 70112
        • Tulane Univ School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Harvard (Massachusetts Gen Hosp)
      • Boston, Massachusetts, United States, 02118
        • Boston Med Ctr
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - West Campus
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med Ctr
      • Springfield, Massachusetts, United States, 01199
        • Baystate Med Ctr of Springfield
      • Worcester, Massachusetts, United States, 01605
        • Med Ctr of Central Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • Univ of Massachusetts Med Ctr
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ of Minnesota
    • Nebraska
      • Omaha, Nebraska, United States, 68105
        • Nebraska Regional Hemophilia Ctr
    • New York
      • Bronx, New York, United States, 10461
        • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
      • Bronx, New York, United States, 10465
        • Jack Weiler Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • Montefiore Med Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10468
        • Bronx Veterans Administration / Mount Sinai Hosp
      • Buffalo, New York, United States, 14215
        • SUNY / Erie County Med Ctr at Buffalo
      • Elmhurst, New York, United States, 11373
        • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
      • New York, New York, United States, 10021
        • Cornell Univ Med Ctr
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr / Peter Krueger Clinic
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10021
        • Mem Sloan - Kettering Cancer Ctr
      • New York, New York, United States, 10025
        • Saint Luke's - Roosevelt Hosp Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Hemophilia Ctr / Mount Sinai Med Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
      • Stony Brook, New York, United States, 117948153
        • SUNY - Stony Brook
      • Syracuse, New York, United States, 13210
        • SUNY / State Univ of New York
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Univ Med Ctr
      • Winston-Salem, North Carolina, United States, 27103
        • Bowman Gray School of Medicine / Wake Forest Univ
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Holmes Hosp / Univ of Cincinnati Med Ctr
      • Cleveland, Ohio, United States, 44106
        • Univ Hosp of Cleveland / Case Western Reserve Univ
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
      • Toledo, Ohio, United States, 43699
        • Med College of Ohio
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 170330850
        • Milton S Hershey Med Ctr
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15219
        • Hemophilia Ctr of Western PA / Univ of Pittsburgh
      • Pittsburgh, Pennsylvania, United States
        • Univ of Pittsburgh Med School
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
    • Texas
      • Houston, Texas, United States, 77030
        • Hermann Hosp / Univ Texas Health Science Ctr
    • Virginia
      • Hampton, Virginia, United States, 23666
        • Dr Stephen L Green
    • Washington
      • Seattle, Washington, United States, 98105
        • Univ of Washington
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Dr Brian Buggy
      • Milwaukee, Wisconsin, United States, 53226
        • Milwaukee County Med Complex
      • Milwaukee, Wisconsin, United States, 53233
        • Great Lakes Hemophilia Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

Required:

  • Aerosolized pentamidine (300 mg every 4 weeks).

Allowed:

  • Chronic suppressive treatment for toxoplasmosis, Pneumocystis carinii pneumonia (PCP), cryptococcal meningitis, herpes simplex virus infection.
  • Ganciclovir for patients developing cytomegalovirus (CMV) infection while in study.
  • Erythropoietin for patients under the relevant treatment IND.
  • Treatment of opportunistic infections with other than sulfonamide-containing regimens.
  • Aspirin, acetaminophen, or non-steroidal anti-inflammatory agents is discouraged, but is permitted for as short a period of time as possible.
  • Chronic use of trimethoprim - sulfamethoxazole or other sulfonamide preparations is not encouraged while on study.

Patients must:

  • Have had the diagnosis of AIDS or advanced AIDS related complex (ARC).
  • Have received AZT therapy for at least 12 months, with a minimal daily dose of 500 mg/day and with no more than 60 days off AZT therapy within the 12 month period; medical records with documentation of AZT dosing must be provided.
  • Provide informed consent (guardian as appropriate).
  • Be available for follow-up for at least 6 months.
  • Have the inclusion laboratory values within approximately 14 days of initiating therapy (except for CD4 cell counts).
  • Patients whose AIDS-defining condition is Kaposi's sarcoma alone must have CD4 cell counts < 300 cells/mm3.

Allowed:

  • Positive blood culture for Mycobacterium avium or Cytomegalovirus.
  • Prior history of toxoplasmosis, Herpes simplex, Cryptococcus, or Pneumocystis carinii pneumonia (PCP) requiring chronic suppressive therapy.
  • Occasional premature atrial or ventricular contractions.

Prior Medication:

Required:

  • Zidovudine (AZT) therapy for at least 12 months, with a minimal daily dose of 500 mg/day, and with no more than 60 days off AZT therapy within the 12-month period (documentation of AZT dosing must be provided).

Allowed:

  • Intralesional agents.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
  • AIDS-dementia complex = or > stage 2.
  • Active AIDS defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • Grade 2 neuropathy, based on the Neuropathy Targeted Symptom Questionnaire, or any moderate abnormality indicative of peripheral neuropathy, particularly impaired sensation of sharp pain, light touch, or vibration in the lower extremities, distal extremity weakness, or distal extremity hyperreflexia.
  • Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • History of past or current heart disease.
  • Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial.
  • Life expectancy < 3 months.

Concurrent Medication:

Excluded:

  • Isoniazid (INH). Neurotoxic drugs. Oral acidifying agents.

Patients with the following are excluded:

  • Psychological or emotional problems sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
  • AIDS-dementia complex = or > stage 2.
  • Active AIDS defining opportunistic infections not specifically allowed.
  • Intractable diarrhea.
  • Prior history of acute pancreatitis within past 2 years or chronic pancreatitis.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • History of past or current heart disease.
  • Malignancy likely in the investigator's opinion to require cytotoxic chemotherapy during the expected course of this trial.
  • Life expectancy = or < 3 months.
  • Previous participation in any study of ddI, ddC or d4T.

Prior Medication:

Excluded:

  • Ganciclovir (DHPG).
  • Excluded within 1 month of study entry:
  • ddI and any other antiretroviral drug or investigational anti-HIV agent except for zidovudine (AZT).

Interferons.

  • Immunomodulating drugs.
  • Cytotoxic agents not specifically allowed.
  • Neurotoxic drugs.

Excluded within 3 months of study entry:

  • Ribavirin.

Prior Treatment:

Excluded within 14 days of study randomization:

  • Blood transfusion.

Active alcohol or drug abuse that is sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 7, 2022

Primary Completion (Actual)

March 1, 1992

Study Completion

December 7, 2022

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)

March 14, 2011

Last Update Submitted That Met QC Criteria

March 11, 2011

Last Verified

August 1, 1992

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 117
  • 070V1
  • AI454-009

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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