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)
NCT ID: NCT00000781
Last Updated: 2021-11-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
1292 participants
INTERVENTIONAL
1996-09-30
Brief Summary
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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.
Detailed Description
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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.
Conditions
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Keywords
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Study Design
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TREATMENT
DOUBLE
Interventions
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Nevirapine
Zidovudine
Zalcitabine
Didanosine
Eligibility Criteria
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Inclusion Criteria
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
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.
13 Years
ALL
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
Glaxo Wellcome
INDUSTRY
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Henry WK
Role: STUDY_CHAIR
Kahn JO
Role: STUDY_CHAIR
Balfour HH
Role: STUDY_CHAIR
Locations
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Univ of Alabama at Birmingham
Birmingham, Alabama, United States
Children's Hosp of Los Angeles
Los Angeles, California, United States
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States
Huntington Memorial Hosp / Children's Hosp of Los Angeles
Pasadena, California, United States
Univ of California / San Diego Treatment Ctr
San Diego, California, United States
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States
San Francisco Gen Hosp
San Francisco, California, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States
Stanford Univ Med Ctr
Stanford, California, United States
Olive View Med Ctr
Sylmar, California, United States
Harbor UCLA Med Ctr
Torrance, California, United States
Denver Dept of Health and Hosps
Denver, Colorado, United States
Mountain States Reg Hemo Ctr / Univ of Colorado
Denver, Colorado, United States
Rose Med Ctr
Denver, Colorado, United States
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States
Yale Univ / New Haven
New Haven, Connecticut, United States
HIV Ctr - District of Columbia Gen Hosp
Washington D.C., District of Columbia, United States
Whitman - Walker Clinic / Georgetown Univ Med Ctr
Washington D.C., District of Columbia, United States
Georgetown Univ Med Ctr
Washington D.C., District of Columbia, United States
George Washington Univ / Hershey Med Ctr
Washington D.C., District of Columbia, United States
Howard Univ
Washington D.C., District of Columbia, United States
Univ of Miami School of Medicine
Miami, Florida, United States
Univ of South Florida
Tampa, Florida, United States
Univ of Hawaii
Honolulu, Hawaii, United States
Northwestern Univ Med School
Chicago, Illinois, United States
Cook County Hosp
Chicago, Illinois, United States
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States
Louis A Weiss Memorial Hosp
Chicago, Illinois, United States
Indiana Univ Hosp
Indianapolis, Indiana, United States
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States
Univ of Louisville / East Tennesee Comprehensive Hem Ctr
Louisville, Kentucky, United States
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States
Boston Med Ctr
Boston, Massachusetts, United States
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
Worcester, Massachusetts, United States
Hennepin County Med Clinic
Minneapolis, Minnesota, United States
Univ of Minnesota
Minneapolis, Minnesota, United States
St Paul Ramsey Med Ctr
Saint Paul, Minnesota, United States
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States
Dartmouth - Hitchcock Med Ctr / Med Ctr Cntrl Massachusetts
Lebanon, New Hampshire, United States
Robert Wood Johnson Med School / Hershey Med Ctr
New Brunswick, New Jersey, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States
Adirondack Med Ctr at Saranac Lake
Albany, New York, United States
Albany Med College / Division of HIV Medicine A158
Albany, New York, United States
Mid - Hudson Care Ctr
Albany, New York, United States
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States
North Shore Univ Hosp
Manhasset, New York, United States
Beth Israel Med Ctr
New York, New York, United States
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States
Saint Clare's Hosp and Health Ctr
New York, New York, United States
Cornell Univ Med Ctr
New York, New York, United States
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States
Mount Sinai Med Ctr / Hemophilia Treatment Ctr
New York, New York, United States
Mount Sinai Med Ctr
New York, New York, United States
Columbia Presbyterian Med Ctr
New York, New York, United States
Harlem Hosp Ctr
New York, New York, United States
Univ of Rochester Medical Center
Rochester, New York, United States
SUNY / State Univ of New York
Syracuse, New York, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
The Bronx, New York, United States
Comprehensive Health Care Ctr / Bronx Municipal Hosp
The Bronx, New York, United States
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
The Bronx, New York, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp
The Bronx, New York, United States
Samaritan Village Inc / Bronx Municipal Hosp
The Bronx, New York, United States
Jack Weiler Hosp / Bronx Municipal Hosp
The Bronx, New York, United States
Montefiore Med Ctr / Bronx Municipal Hosp
The Bronx, New York, United States
Montefiore Med Ctr Adolescent AIDS Program
The Bronx, New York, United States
North Central Bronx Hosp / Bronx Municipal Hosp
The Bronx, New York, United States
Bronx Veterans Administration / Mount Sinai Hosp
The Bronx, New York, United States
Univ of North Carolina
Chapel Hill, North Carolina, United States
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States
Univ of Cincinnati
Cincinnati, Ohio, United States
Univ of Kentucky Lexington
Cincinnati, Ohio, United States
Case Western Reserve Univ
Cleveland, Ohio, United States
MetroHealth Med Ctr
Cleveland, Ohio, United States
Columbus Children's Hosp
Columbus, Ohio, United States
Med College of Ohio
Toledo, Ohio, United States
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States
Saint Michael's Med Ctr / Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States
Girard Med Ctr
Philadelphia, Pennsylvania, United States
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States
Med Univ of South Carolina / UNC
Charleston, South Carolina, United States
Julio Arroyo
West Columbia, South Carolina, United States
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
Knoxville, Tennessee, United States
Meharry Med College
Nashville, Tennessee, United States
Univ of Texas Galveston
Galveston, Texas, United States
Univ Texas Health Science Ctr / Univ Texas Med School
Houston, Texas, United States
Univ of Washington
Seattle, Washington, United States
Northern Wisconsin Hemophilia Ctr / Saint Vincent's Hosp
Green Bay, Wisconsin, United States
Great Lakes Hemophilia Foundation
Wauwatosa, Wisconsin, United States
Univ of Puerto Rico
San Juan, , Puerto Rico
Countries
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References
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Henry K, Erice A, Tierney C, Balfour HH Jr, Fischl MA, Kmack A, Liou SH, Kenton A, Hirsch MS, Phair J, Martinez A, Kahn JO. A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS. AIDS Clinical Trial Group 193A Study Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Dec 1;19(4):339-49. doi: 10.1097/00042560-199812010-00004.
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)
Price RW, Yiannoutsos CT, Clifford DB, Zaborski L, Tselis A, Sidtis JJ, Cohen B, Hall CD, Erice A, Henry K. Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium study team. AIDS. 1999 Sep 10;13(13):1677-85. doi: 10.1097/00002030-199909100-00011.
Other Identifiers
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11169
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG 193A
Identifier Type: -
Identifier Source: org_study_id