A Randomized, Double-Blind, Four-Arm Study Comparing Combination Nucleoside, Alternating Nucleoside, and Triple-Drug Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3)

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000781
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

To determine the relative clinical efficacy of zidovudine ( AZT ) plus didanosine (ddI), AZT plus zalcitabine ( ddC ), AZT alternating monthly with ddI, and AZT/ddI plus nevirapine in HIV-infected patients with advanced disease.

The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Four-Arm Study Comparing Combination Nucleoside, Alternating Nucleoside, and Triple-Drug Therapy for the Treatment of Advanced HIV Disease (CD4 <= 50/mm3)

Resource links provided by NLM:


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

Estimated Enrollment: 1292
Study Completion Date: September 1996
Detailed Description:

The rapid emergence of resistant HIV strains has been observed in patients receiving monotherapy with a nucleoside analog or non-nucleoside reverse transcriptase inhibitor. Use of combination therapy with two nucleoside drugs or convergent combination therapy with two nucleosides and a non-nucleoside RT inhibitor may minimize the evolution of these resistant HIV strains. Since toxicity is a major problem in patients with advanced disease who are receiving combination nucleoside therapy, alternating the two drugs may provide a way of retaining several benefits of combination therapy while minimizing the increased toxicity.

Patients are randomized to receive either AZT/ddC, AZT/ddI, AZT alternating monthly with ddI, or AZT/ddI/nevirapine. Patients are evaluated at week 0 and every 4 weeks thereafter for 2 years. Pharmacologic, virologic, and macroneurologic substudies will be conducted. Patients who are already enrolled on protocol ACTG 193 will be given the option of continuing on their originally assigned ACTG 193 therapy for an additional 6 months or undergoing re-randomization to one of the four treatment arms on ACTG 193A.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis.

Allowed:

  • Erythropoietin maintenance.
  • G-CSF and GM-CSF.
  • Prophylaxis for Mycobacterium avium intracellulare.
  • Antifungal prophylaxis or treatment with specific drugs.
  • Maintenance therapy for opportunistic infection.
  • Over-the-counter medications or alternative therapies such as vitamins and herbs.
  • Antibiotics as clinically indicated.
  • Steroids for < 21 days for acute problems.
  • Antipyretics, analgesics, allergy medication, antidepressants, sleep medications, oral contraceptives, or other appropriate medications.

Concurrent Treatment:

Allowed:

  • Radiation therapy for cutaneous Kaposi's sarcoma.
  • Acupuncture.

Patients must have:

  • Documented HIV infection.
  • CD4 count <= 50 cells/mm3.
  • Either no prior nucleoside therapy OR a history of prior nucleoside therapy in the absence of high-grade intolerance.
  • Life expectancy of at least 6 months.
  • Consent of parent or guardian if < 18 years of age.
  • Normal chest x-ray at baseline or within 6 months prior to study entry in the absence of new pulmonary or cardiac symptoms (per 12/28/94 amendment).

NOTE:

  • Patients who withdrew from protocol ACTG 193 therapy prior to activation of ACTG 193A are not eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Abnormal baseline chest x-ray.
  • New pulmonary or cardiac symptoms.
  • Psychological or emotional problems sufficient to prevent compliance with study medication.

Concurrent Medication:

Excluded:

  • Systemic chemotherapy for malignancy.
  • Acute or induction therapy for opportunistic infection.
  • Antiretroviral drugs other than study drugs.
  • Biological response modifiers.
  • Erythromycin, phenytoin, phenobarbital, warfarin, or coumadin.

Patients with the following prior conditions are excluded:

  • History of recurrent grade 3 or greater toxicity to AZT, ddI, or ddC on two or more occasions.
  • Evidence of active pulmonary disease within 6 months prior to study entry.
  • History of grade 3 or worse peripheral neuropathy.
  • History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

  • Prior nevirapine.

Excluded within 7 days prior to study entry:

  • Acute therapy for opportunistic infection (maintenance therapy is permitted).
  • Acute systemic therapy for a nonopportunistic infection or other medical condition.
  • Antiretroviral drugs other than AZT, ddI, or ddC.
  • Biological response modifiers.
  • d4T therapy.
  • Nucleosides other than those used in the study.
  • Antibiotics containing clavulanate potassium.

Prior Treatment:

Excluded:

  • More than 4 units of blood in a 30-day period.

Active alcohol or drug abuse.

  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: NCT00000781

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Children's Hosp of Los Angeles
Los Angeles, California, United States, 90027
Huntington Memorial Hosp / Children's Hosp of Los Angeles
Pasadena, California, United States, 91105
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
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Olive View Med Ctr
Sylmar, California, United States, 91342
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, Colorado
Mountain States Reg Hemo Ctr / Univ of Colorado
Denver, Colorado, United States, 80262
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
Denver Dept of Health and Hosps
Denver, Colorado, United States, 80262
Rose Med Ctr
Denver, Colorado, United States, 80262
United States, Connecticut
Yale Univ / New Haven
New Haven, Connecticut, United States, 065102483
United States, District of Columbia
Howard Univ
Washington, District of Columbia, United States, 20059
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
Whitman - Walker Clinic / Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 200072197
HIV Ctr - District of Columbia Gen Hosp
Washington, District of Columbia, United States, 200072197
George Washington Univ / Hershey Med Ctr
Washington, District of Columbia, United States, 20037
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
Univ of South Florida
Tampa, Florida, United States, 33612
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Cook County Hosp
Chicago, Illinois, United States, 60612
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Louis A Weiss Memorial Hosp
Chicago, Illinois, United States, 60640
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Univ of Louisville / East Tennesee Comprehensive Hem Ctr
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
Worcester, Massachusetts, United States, 01605
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
Hennepin County Med Clinic
Minneapolis, Minnesota, United States, 55415
St Paul Ramsey Med Ctr
St Paul, Minnesota, United States, 55101
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New Hampshire
Dartmouth - Hitchcock Med Ctr / Med Ctr Cntrl Massachusetts
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Robert Wood Johnson Med School / Hershey Med Ctr
New Brunswick, New Jersey, United States, 08903
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
United States, New York
Adirondack Med Ctr at Saranac Lake
Albany, New York, United States, 122083479
Albany Med College / Division of HIV Medicine A158
Albany, New York, United States, 122083479
Mid - Hudson Care Ctr
Albany, New York, United States, 122083479
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Comprehensive Health Care Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Montefiore Med Ctr Adolescent AIDS Program
Bronx, New York, United States, 10467
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
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
North Shore Univ Hosp
Manhasset, New York, United States, 11030
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Harlem Hosp Ctr
New York, New York, United States, 10037
Saint Clare's Hosp and Health Ctr
New York, New York, United States, 10019
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mount Sinai Med Ctr / Hemophilia Treatment Ctr
New York, New York, United States, 10029
Mount Sinai Med Ctr
New York, New York, United States, 10029
Columbia Presbyterian Med Ctr
New York, New York, United States, 100323784
Beth Israel Med Ctr
New York, New York, United States, 10003
Cornell Univ Med Ctr
New York, New York, United States, 10021
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
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
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Univ of Kentucky Lexington
Cincinnati, Ohio, United States, 45267
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Columbus Children's Hosp
Columbus, Ohio, United States, 432052696
Med College of Ohio
Toledo, Ohio, United States, 43699
United States, Pennsylvania
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
Saint Michael's Med Ctr / Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
Girard Med Ctr
Philadelphia, Pennsylvania, United States, 191046073
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Med Univ of South Carolina / UNC
Charleston, South Carolina, United States, 29425
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
Meharry Med College
Nashville, Tennessee, United States, 37203
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
Univ Texas Health Science Ctr / Univ Texas Med School
Houston, Texas, United States, 77030
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
United States, Wisconsin
Northern Wisconsin Hemophilia Ctr / Saint Vincent's Hosp
Green Bay, Wisconsin, United States, 54301
Great Lakes Hemophilia Foundation
Wauwatosa, Wisconsin, United States, 532130127
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: Henry WK
Study Chair: Kahn JO
Study Chair: Balfour HH
  More Information

Additional Information:
Publications:
Price RW, Yiannoutsos C, Zaborski L, Kmack A, Henry K, Tierney C, Clifford D. Neurological substudies of ACTG protocol 193A: quantitative neurological performance measures and treatment outcomes. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:176 (abstract no 516)
Robinson P, Cotton D, Curry R, Henry K, Hall D, Myers M. Analysis of nevirapine (NVP) effect on clinical endpoints (CEs) of HIV progression or death in ACTG trial 193A. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:210 (abstract no 700)
Henry K, Tierney C, Kahn J, Balfour H, Jiang Q, Kmack A, Fischl M. A randomized, double-blind, placebo-controlled study comparing combination nucleoside and triple therapy for the treatment of advanced HIV disease (CD4 less than or equal to 50/mm(3)). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:207 (abstract no LB6)
Coplan P, Nikas A, Saah A, Nessly M, Doll L, Leavitt R, Benson J, Guess H. No association observed between indinavir therapy for HIV/AIDS and myocardial infarction in 4 clinical trials with 2,825 subjects. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:191 (abstract no 658)
Erice A, Tierney C, Balfour HH Jr, Liou S, Kahn JO, Henry WK. Virologlc effect of therapy with reverse transcriptase inhibitors (RTIs) in patients with AIDS and less than 50 CD4+ T cells per mm(3): a substudy of ACTG 193a. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:204 (abstract no 662)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000781     History of Changes
Other Study ID Numbers: ACTG 193A, 11169
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Nevirapine

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
Didanosine
Zidovudine
Nevirapine
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