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Evaluation of Patients Who Have Not Had Success With Zidovudine

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
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 Virus Replication, Didanosine, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine

Eligibility Criteria

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

Inclusion Criteria Concurrent Medication: Allowed: Chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), Mycobacterium tuberculosis, or Herpes simplex virus, or against other opportunistic infections as indicated. Corticosteroids for no longer than 21 days (only as part of PCP therapy). Erythropoietin and G-CSF. Patients must have: Documented HIV-seropositivity. CD4 count 100 - 300 cells/mm3. Prior continuous AZT dose = or > 300 mg/day for 1 year or longer. Prior Medication: Required: AZT for at least 1 year prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Medical contraindication or is considered noncompliant in the opinion of the investigator. Peripheral neuropathy = or > grade 2. Concurrent Medication: Excluded: Anti-HIV agents other than study drugs. Biologic response modifiers (other than erythropoietin or G-CSF). Systemic cytotoxic chemotherapy. Regularly prescribed medications (such as antipyretics, analgesics, allergy medications) that are associated with an increased risk of pancreatitis, peripheral neuropathy, or bone marrow suppression. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following prior conditions are excluded: History of acute or chronic pancreatitis, gout, or uric acid nephropathy. Prior Medication: Excluded: Other antiretrovirals besides AZT. ddI or ddC for more than 30 days within the past year or any time within 3 months prior to study entry. Acute therapy for an infection or other medical illness within 14 days prior to study entry.

Sites / Locations

  • Univ of Alabama at Birmingham
  • San Francisco Gen Hosp
  • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
  • San Mateo AIDS Program / Stanford Univ
  • Kaiser Permanente Franklin Med Ctr
  • Univ of Colorado Health Sciences Ctr
  • Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
  • Northwestern Univ Med School
  • Cook County Hosp
  • Rush Presbyterian - Saint Luke's Med Ctr
  • Baystate Med Ctr of Springfield
  • Univ of Minnesota
  • Univ of Nebraska Med Ctr
  • SUNY / Health Sciences Ctr at Brooklyn
  • SUNY / Erie County Med Ctr at Buffalo
  • Univ of Rochester Medical Center
  • SUNY / State Univ of New York
  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00001025
Brief Title
Evaluation of Patients Who Have Not Had Success With Zidovudine
Official Title
A Study to Evaluate the Short-Term Clinical and Virologic Significance of Zidovudine Resistance
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 1995 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
To determine the relationship of viral susceptibility to zidovudine (AZT) and baseline viral load (as determined by plasma viremia and quantitative endpoint dilution). To determine the relationship between viral load and susceptibility during different antiretroviral therapy strategies. To correlate measures of viral load and short term clinical and laboratory markers (such as weight, CD4 count, p24 antigenemia, and beta2 microglobulin) on the different therapy arms. High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.
Detailed Description
High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors. One hundred-twenty patients who have been receiving AZT for at least 1 year are randomized to 1) continue with AZT, 2) switch to treatment with didanosine at 1 of 2 doses, or 3) receive both AZT and ddI. Treatment is given for 16 weeks, with a possible extension to 32 weeks. Patients are followed at weeks 2, 4, 8, 12, and 16. For analysis purposes only, patients are stratified according to degree of susceptibility of HIV isolates to AZT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Virus Replication, Didanosine, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine

7. Study Design

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

8. Arms, Groups, and Interventions

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: Allowed: Chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), Mycobacterium tuberculosis, or Herpes simplex virus, or against other opportunistic infections as indicated. Corticosteroids for no longer than 21 days (only as part of PCP therapy). Erythropoietin and G-CSF. Patients must have: Documented HIV-seropositivity. CD4 count 100 - 300 cells/mm3. Prior continuous AZT dose = or > 300 mg/day for 1 year or longer. Prior Medication: Required: AZT for at least 1 year prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Medical contraindication or is considered noncompliant in the opinion of the investigator. Peripheral neuropathy = or > grade 2. Concurrent Medication: Excluded: Anti-HIV agents other than study drugs. Biologic response modifiers (other than erythropoietin or G-CSF). Systemic cytotoxic chemotherapy. Regularly prescribed medications (such as antipyretics, analgesics, allergy medications) that are associated with an increased risk of pancreatitis, peripheral neuropathy, or bone marrow suppression. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following prior conditions are excluded: History of acute or chronic pancreatitis, gout, or uric acid nephropathy. Prior Medication: Excluded: Other antiretrovirals besides AZT. ddI or ddC for more than 30 days within the past year or any time within 3 months prior to study entry. Acute therapy for an infection or other medical illness within 14 days prior to study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Corey L
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Cavert W
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Coombs R
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
City
San Jose
State/Province
California
ZIP/Postal Code
951282699
Country
United States
Facility Name
San Mateo AIDS Program / Stanford Univ
City
Stanford
State/Province
California
ZIP/Postal Code
943055107
Country
United States
Facility Name
Kaiser Permanente Franklin Med Ctr
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Univ of Colorado Health Sciences Ctr
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Northwestern Univ Med School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Presbyterian - Saint Luke's Med Ctr
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Baystate Med Ctr of Springfield
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Univ of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Univ of Nebraska Med Ctr
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
681985130
Country
United States
Facility Name
SUNY / Health Sciences Ctr at Brooklyn
City
Brooklyn
State/Province
New York
ZIP/Postal Code
112032098
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY / State Univ of New York
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
981224304
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Cavert W, Coombs RW, Kuritzkes D, Grimes J, Stein D, Rojo W, Beatty C, Winters M, Corey L. Baseline zidovudine (ZDV) susceptibility, codon 215 mutation, viral load and syncytium-inducting characteristics(SI) of HIV isolates from ACTG protocol 194. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:137
Results Reference
background
Citation
Reichelderfer PS, Coombs RW. Multifactorial analysis of the inverse relationship between viral load and CD4+ cell count. Int Conf AIDS. 1996 Jul 7-12;11(2):277 (abstract no ThB4148)
Results Reference
background

Learn more about this trial

Evaluation of Patients Who Have Not Had Success With Zidovudine

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