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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000671
First received: November 2, 1999
Last updated: March 11, 2011
Last verified: August 1992
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Didanosine
Phase 2

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Estimated Enrollment: 750
Primary Completion Date: March 1992 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000671

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

Additional Information:
Publications:
Kozal M, Winters M, Shafer R, Kroodsma K, Katzenstein D, Merigan T. Behavior of codon 74 and 215 pol gene mutations in 62 AZT experienced patients on ddI monotherapy. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;55

ClinicalTrials.gov Identifier: NCT00000671     History of Changes
Other Study ID Numbers: ACTG 117, 070V1, AI454-009
Study First Received: November 2, 1999
Last Updated: March 11, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
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
Didanosine
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 August 26, 2014