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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lamivudine
Stavudine
Zidovudine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Didanosine, Drug Therapy, Combination, AIDS-Related Complex, Antiviral Agents, Zidovudine, Stavudine, Lamivudine, Drug Combinations

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Alabama Therapeutics CRS
  • USC CRS
  • UCLA CARE Center CRS
  • Stanford CRS
  • Ucsd, Avrc Crs
  • Ucsf Aids Crs
  • Santa Clara Valley Med. Ctr.
  • San Mateo County AIDS Program
  • Harbor-UCLA Med. Ctr. CRS
  • University of Colorado Hospital CRS
  • Univ. of Miami AIDS CRS
  • Emory Univ. Hemophilia Program Office
  • Northwestern University CRS
  • Cook County Hosp. CORE Ctr.
  • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Tulane Hemophilia Treatment Ctr.
  • Johns Hopkins Adult AIDS CRS
  • Massachusetts General Hospital ACTG CRS
  • Bmc Actg Crs
  • Beth Israel Deaconess - East Campus A0102 CRS
  • Beth Israel Deaconess Med. Ctr., ACTG CRS
  • University of Minnesota, ACTU
  • St. Louis ConnectCare, Infectious Diseases Clinic
  • Washington U CRS
  • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
  • SUNY - Buffalo, Erie County Medical Ctr.
  • NY Univ. HIV/AIDS CRS
  • Cornell University A2201
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • Carolinas HealthCare System, Carolinas Med. Ctr.
  • Regional Center for Infectious Disease, Wendover Medical Center CRS
  • Univ. of Cincinnati CRS
  • Case CRS
  • The Ohio State Univ. AIDS CRS
  • Hosp. of the Univ. of Pennsylvania CRS
  • University of Washington AIDS CRS
  • Puerto Rico-AIDS CRS
  • Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000831
Brief Title
Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy
Official Title
Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1998 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Didanosine, Drug Therapy, Combination, AIDS-Related Complex, Antiviral Agents, Zidovudine, Stavudine, Lamivudine, Drug Combinations

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
280 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Lamivudine
Intervention Type
Drug
Intervention Name(s)
Stavudine
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katzenstein D
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hammer S
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
USC CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford CRS
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Ucsd, Avrc Crs
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
Country
United States
Facility Name
Santa Clara Valley Med. Ctr.
City
San Jose
State/Province
California
Country
United States
Facility Name
San Mateo County AIDS Program
City
San Mateo
State/Province
California
Country
United States
Facility Name
Harbor-UCLA Med. Ctr. CRS
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
Country
United States
Facility Name
Emory Univ. Hemophilia Program Office
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30365
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp. CORE Ctr.
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Tulane Hemophilia Treatment Ctr.
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Bmc Actg Crs
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Beth Israel Deaconess Med. Ctr., ACTG CRS
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Minnesota, ACTU
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
St. Louis ConnectCare, Infectious Diseases Clinic
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell University A2201
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Carolinas HealthCare System, Carolinas Med. Ctr.
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Regional Center for Infectious Disease, Wendover Medical Center CRS
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Puerto Rico-AIDS CRS
City
San Juan
Country
Puerto Rico
Facility Name
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
City
Mbeya
Country
Tanzania

12. IPD Sharing Statement

Citations:
PubMed Identifier
11468426
Citation
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.
Results Reference
background
PubMed Identifier
10933617
Citation
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.
Results Reference
background
PubMed Identifier
12394789
Citation
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.
Results Reference
background

Learn more about this trial

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

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