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AzTrials

HIV InfectionsPhase 2NCT00000781

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)

A Phase 2 study testing Nevirapine, Zidovudine and Zalcitabine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 96 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 13 years and older
Conditions the study is for
HIV Infections
What is being tested?
Nevirapine, Zidovudine and Zalcitabine
How many people
1,292 participants
Where
96 sitesin 2 countries
Study dates
Start not givento Sep 1996
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Required:
  • PCP prophylaxis.
  • Allowed:
  • Erythropoietin maintenance.
  • G-CSF and GM-CSF.
Show all 26Show fewer
  • 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.

Who cannot join

  • 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:
Show all 32Show fewer
  • 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.

Trial locations and contacts

96 sites in 2 countries.

96 sites in 2 countries

United States95 sites

  • Adirondack Med Ctr at Saranac Lake

    Albany, New York, 122083479

  • Albany Med College / Division of HIV Medicine A158

    Albany, New York, 122083479

  • Mid - Hudson Care Ctr

    Albany, New York, 122083479

  • Univ of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Harvard (Massachusetts Gen Hosp)

    Boston, Massachusetts, 02114

  • Boston Med Ctr

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess - West Campus

    Boston, Massachusetts, 02215

  • SUNY / Health Sciences Ctr at Brooklyn

    Brooklyn, New York, 112032098

  • SUNY / Erie County Med Ctr at Buffalo

    Buffalo, New York, 14215

  • Univ of North Carolina

    Chapel Hill, North Carolina, 275997215

  • Med Univ of South Carolina / UNC

    Charleston, South Carolina, 29425

  • Northwestern Univ Med School

    Chicago, Illinois, 60611

  • Cook County Hosp

    Chicago, Illinois, 60612

  • Rush Presbyterian - Saint Luke's Med Ctr

    Chicago, Illinois, 60612

  • Louis A Weiss Memorial Hosp

    Chicago, Illinois, 60640

  • Univ of Cincinnati

    Cincinnati, Ohio, 452670405

  • Univ of Kentucky Lexington

    Cincinnati, Ohio, 45267

  • Case Western Reserve Univ

    Cleveland, Ohio, 44106

  • MetroHealth Med Ctr

    Cleveland, Ohio, 441091998

  • Columbus Children's Hosp

    Columbus, Ohio, 432052696

  • Denver Dept of Health and Hosps

    Denver, Colorado, 80262

  • Mountain States Reg Hemo Ctr / Univ of Colorado

    Denver, Colorado, 80262

  • Rose Med Ctr

    Denver, Colorado, 80262

  • Univ of Colorado Health Sciences Ctr

    Denver, Colorado, 80262

  • City Hosp Ctr at Elmhurst / Mount Sinai Hosp

    Elmhurst, New York, 11373

  • Univ of Texas Galveston

    Galveston, Texas, 775550435

  • Northern Wisconsin Hemophilia Ctr / Saint Vincent's Hosp

    Green Bay, Wisconsin, 54301

  • Moses H Cone Memorial Hosp

    Greensboro, North Carolina, 27401

  • Milton S Hershey Med Ctr

    Hershey, Pennsylvania, 170330850

  • Saint Michael's Med Ctr / Milton S Hershey Med Ctr

    Hershey, Pennsylvania, 170330850

  • Univ of Hawaii

    Honolulu, Hawaii, 96816

  • Univ Texas Health Science Ctr / Univ Texas Med School

    Houston, Texas, 77030

  • Indiana Univ Hosp

    Indianapolis, Indiana, 462025250

  • Methodist Hosp of Indiana / Life Care Clinic

    Indianapolis, Indiana, 46202

  • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

    Knoxville, Tennessee, 37920

  • Dartmouth - Hitchcock Med Ctr / Med Ctr Cntrl Massachusetts

    Lebanon, New Hampshire, 03756

  • Children's Hosp of Los Angeles

    Los Angeles, California, 90027

  • Univ of Southern California / LA County USC Med Ctr

    Los Angeles, California, 900331079

  • Univ of Louisville / East Tennesee Comprehensive Hem Ctr

    Louisville, Kentucky, 40202

  • North Shore Univ Hosp

    Manhasset, New York, 11030

  • Univ of Miami School of Medicine

    Miami, Florida, 331361013

  • Hennepin County Med Clinic

    Minneapolis, Minnesota, 55415

  • Univ of Minnesota

    Minneapolis, Minnesota, 55455

  • Meharry Med College

    Nashville, Tennessee, 37203

  • Robert Wood Johnson Med School / Hershey Med Ctr

    New Brunswick, New Jersey, 08903

  • Yale Univ / New Haven

    New Haven, Connecticut, 065102483

  • Beth Israel Med Ctr

    New York, New York, 10003

  • Bellevue Hosp / New York Univ Med Ctr

    New York, New York, 10016

  • Saint Clare's Hosp and Health Ctr

    New York, New York, 10019

  • Cornell Univ Med Ctr

    New York, New York, 10021

  • Mem Sloan - Kettering Cancer Ctr

    New York, New York, 10021

  • Mount Sinai Med Ctr / Hemophilia Treatment Ctr

    New York, New York, 10029

  • Mount Sinai Med Ctr

    New York, New York, 10029

  • Columbia Presbyterian Med Ctr

    New York, New York, 100323784

  • Harlem Hosp Ctr

    New York, New York, 10037

  • Univ of Medicine & Dentistry of New Jersey / Univ Hosp

    Newark, New Jersey, 071032714

  • Univ of Nebraska Med Ctr

    Omaha, Nebraska, 681985130

  • Huntington Memorial Hosp / Children's Hosp of Los Angeles

    Pasadena, California, 91105

  • Girard Med Ctr

    Philadelphia, Pennsylvania, 191046073

  • Univ of Pennsylvania at Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson Univ Hosp

    Philadelphia, Pennsylvania, 191075098

  • Univ of Rochester Medical Center

    Rochester, New York, 14642

  • St Paul Ramsey Med Ctr

    Saint Paul, Minnesota, 55101

  • Univ of California / San Diego Treatment Ctr

    San Diego, California, 921036325

  • San Francisco AIDS Clinic / San Francisco Gen Hosp

    San Francisco, California, 941102859

  • San Francisco Gen Hosp

    San Francisco, California, 941102859

  • Stanford at Kaiser / Kaiser Permanente Med Ctr

    San Francisco, California, 94115

  • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

    San Jose, California, 951282699

  • Univ of Washington

    Seattle, Washington, 981224304

  • St Louis Regional Hosp / St Louis Regional Med Ctr

    St Louis, Missouri, 63112

  • San Mateo AIDS Program / Stanford Univ

    Stanford, California, 943055107

  • Stanford Univ Med Ctr

    Stanford, California, 943055107

  • Olive View Med Ctr

    Sylmar, California, 91342

  • SUNY / State Univ of New York

    Syracuse, New York, 13210

  • Univ of South Florida

    Tampa, Florida, 33612

  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr

    The Bronx, New York, 10461

  • Comprehensive Health Care Ctr / Bronx Municipal Hosp

    The Bronx, New York, 10461

  • Montefiore Drug Treatment Ctr / Bronx Municipal Hosp

    The Bronx, New York, 10461

  • Montefiore Family Health Ctr / Bronx Municipal Hosp

    The Bronx, New York, 10461

  • Samaritan Village Inc / Bronx Municipal Hosp

    The Bronx, New York, 10461

  • Jack Weiler Hosp / Bronx Municipal Hosp

    The Bronx, New York, 10465

  • Montefiore Med Ctr / Bronx Municipal Hosp

    The Bronx, New York, 10467

  • Montefiore Med Ctr Adolescent AIDS Program

    The Bronx, New York, 10467

  • North Central Bronx Hosp / Bronx Municipal Hosp

    The Bronx, New York, 10467

  • Bronx Veterans Administration / Mount Sinai Hosp

    The Bronx, New York, 10468

  • Med College of Ohio

    Toledo, Ohio, 43699

  • Harbor UCLA Med Ctr

    Torrance, California, 90502

  • HIV Ctr - District of Columbia Gen Hosp

    Washington D.C., District of Columbia, 200072197

  • Whitman - Walker Clinic / Georgetown Univ Med Ctr

    Washington D.C., District of Columbia, 200072197

  • Georgetown Univ Med Ctr

    Washington D.C., District of Columbia, 20007

  • George Washington Univ / Hershey Med Ctr

    Washington D.C., District of Columbia, 20037

  • Howard Univ

    Washington D.C., District of Columbia, 20059

  • Great Lakes Hemophilia Foundation

    Wauwatosa, Wisconsin, 532130127

  • Julio Arroyo

    West Columbia, South Carolina, 29169

  • Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial

    Worcester, Massachusetts, 01605

Other trials in United States

Puerto Rico1 site

  • Univ of Puerto Rico

    San Juan, 009365067

Other trials in Puerto Rico

About this study

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.

Read the 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.

Conditions
HIV Infections
Being tested
Nevirapine, Zidovudine, Zalcitabine, Didanosine
Keywords
Zalcitabine, Didanosine, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, Zidovudine, Nevirapine
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NevirapineDrug

  • ZidovudineDrug

  • ZalcitabineDrug

  • DidanosineDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionSep 1996

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Masking
Double blind
Enrolment
1,292 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000781
Sponsor's protocol ID
ACTG 193A
Other IDs
11169
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
4 Nov 2021
Results posted
No

Publications

  • 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.

    PubMed 9833742

  • 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.

    PubMed 10509569

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nevirapine, Zidovudine and Zalcitabine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 96 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 96 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000781, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.

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Clinical Trial NCT00000781 | AzTrials