Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy

NCT ID: NCT00000831

Last Updated: 2021-11-04

Study Results

Results pending

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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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1998-05-31

Brief Summary

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To elucidate the relationship between virologic risk factors and immunologic and clinical progression in patients receiving monotherapy in protocol ACTG 175, and to compare new treatment regimens with combinations of reverse transcriptase inhibitors in long-term recipients of monotherapy. Specifically, to determine, in patients who have been taking zidovudine (AZT) alone for a long time, whether it is beneficial to add lamivudine (3TC) to AZT or to switch to d4T alone, and also to determine, in patients who have been taking didanosine (ddI) alone for a long time, whether it is beneficial to add AZT or AZT/3TC to ddI.

Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Detailed Description

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Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Patients with prior AZT experience only are randomized to receive either d4T alone or AZT/3TC. Patients with prior ddI experience only are randomized to receive ddI/AZT or ddI/AZT/3TC. PER AMENDMENT 8/27/96: The study has been extended 6 months and treatment will be available until March 15, 1997 at the latest. Each patient will have regularly scheduled 12 week safety visits during the extension period.

AS PER AMENDMENT 1/22/97: The study has been extended for approximately 16 additional weeks beyond the current 6-month extension. Subjects will be unblinded to their assigned regimen beginning 2/21/97 and will continue therapy for up to 16 weeks in open-label fashion. AS PER AMENDMENT 5/9/97: The study has been extended for an additional 8 weeks; study drug will not be provided after 9/15/97.

Conditions

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HIV Infections

Keywords

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Didanosine Drug Therapy, Combination AIDS-Related Complex Antiviral Agents Zidovudine Stavudine Lamivudine Drug Combinations

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Lamivudine

Intervention Type DRUG

Stavudine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Concurrent Medication:

Recommended:

* PCP prophylaxis in patients with CD4 count \<= 200 cells/mm3.

Allowed:

* Chemophylaxis against Mycobacterium tuberculosis.
* Acyclovir.
* Vaccination with pneumococcal vaccine polyvalent.
* Haemophilus B Conjugate vaccine.
* Chemoprophylaxis for MAC and Toxoplasma gondii.
* Antibiotics.
* Recombinant erythropoietin ( EPO ) and G-CSF.
* Systemic corticosteroids for \< 21 days.
* Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, and oral contraceptives.
* Vitamins and herbal therapies.

Concurrent Treatment:

Allowed:

* Limited local radiation therapy to skin.
* Blood transfusions if 3 units or less per 21-day period.
* Acupuncture.
* Visualization techniques.

Patients must have:

* Completed AZT or ddI monotherapy on ACTG 175 and remained on that regimen during any subsequent interval.
* Not reached an ACTG 175 endpoint prior to May 1, 1995.
* Consent of parent or guardian if less than 18 years old.

PER AMENDMENT 8/27/96:

* Patients must be on study/on treatment at the time the protocol study treatment is extended.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Grade 2 or worse peripheral neuropathy.
* Malignancy requiring systemic therapy.

Concurrent Medication:

Excluded:

* Anti-HIV drugs other than study drugs.
* Biologic response modifiers.
* Systemic cytotoxic chemotherapy.
* Any drug known to affect glucuronidation and/or clearance of AZT.

Concurrent Treatment:

Excluded:

* Radiation therapy other than limited local therapy to skin.

Patients with the following prior condition are excluded:

* History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

* Prior 3TC.
* Acute therapy for an infection (other than HIV) or other medical illness within 14 days prior to study entry.

Current ethanol abuse.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katzenstein D

Role: STUDY_CHAIR

Hammer S

Role: STUDY_CHAIR

Locations

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Alabama Therapeutics CRS

Birmingham, Alabama, United States

Site Status

USC CRS

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Stanford CRS

Palo Alto, California, United States

Site Status

Ucsd, Avrc Crs

San Diego, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

Santa Clara Valley Med. Ctr.

San Jose, California, United States

Site Status

San Mateo County AIDS Program

San Mateo, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Emory Univ. Hemophilia Program Office

Atlanta, Georgia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Tulane Hemophilia Treatment Ctr.

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

Omaha, Nebraska, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Cornell University A2201

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Carolinas HealthCare System, Carolinas Med. Ctr.

Charlotte, North Carolina, United States

Site Status

Regional Center for Infectious Disease, Wendover Medical Center CRS

Greensboro, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Puerto Rico-AIDS CRS

San Juan, , Puerto Rico

Site Status

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, , Tanzania

Site Status

Countries

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United States Puerto Rico Tanzania

References

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Shulman NS, Machekano RA, Shafer RW, Winters MA, Zolopa AR, Liou SH, Hughes M, Katzenstein DA; AIDS Clinical Trials Group 302 Study Team. Genotypic correlates of a virologic response to stavudine after zidovudine monotherapy. J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):377-80. doi: 10.1097/00126334-200108010-00008.

Reference Type BACKGROUND
PMID: 11468426 (View on PubMed)

Katzenstein DA, Hughes M, Albrecht M, Hammer S, Para M, Murphy R, Valdez H, Haubrich R, Liou S. Virologic and CD4+ cell responses to new nucleoside regimens: switching to stavudine or adding lamivudine after prolonged zidovudine treatment of human immunodeficiency virus infection. ACTG 302 Study Team. AIDS Clinical Trials Group. AIDS Res Hum Retroviruses. 2000 Jul 20;16(11):1031-7. doi: 10.1089/08892220050075282.

Reference Type BACKGROUND
PMID: 10933617 (View on PubMed)

Shulman NS, Hughes MD, Winters MA, Shafer RW, Zolopa AR, Hellmann NS, Bates M, Whitcomb JM, Katzenstein DA. Subtle decreases in stavudine phenotypic susceptibility predict poor virologic response to stavudine monotherapy in zidovudine-experienced patients. J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):121-7. doi: 10.1097/00126334-200210010-00001.

Reference Type BACKGROUND
PMID: 12394789 (View on PubMed)

Other Identifiers

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11277

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 302

Identifier Type: -

Identifier Source: org_study_id