Evaluation of Patients Who Have Not Had Success With Zidovudine

NCT ID: NCT00001025

Last Updated: 2021-11-01

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

120 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1995-05-31

Brief Summary

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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

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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.

Conditions

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HIV Infections

Keywords

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Virus Replication Didanosine Acquired Immunodeficiency Syndrome AIDS-Related Complex Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Zidovudine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Glaxo Wellcome

INDUSTRY

Sponsor Role collaborator

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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Corey L

Role: STUDY_CHAIR

Cavert W

Role: STUDY_CHAIR

Coombs R

Role: STUDY_CHAIR

Locations

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Univ of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

San Francisco Gen Hosp

San Francisco, California, United States

Site Status

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

San Jose, California, United States

Site Status

San Mateo AIDS Program / Stanford Univ

Stanford, California, United States

Site Status

Kaiser Permanente Franklin Med Ctr

Denver, Colorado, United States

Site Status

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Site Status

Children's Mem Hosp Family Cln / Northwestern Univ Med Schl

Chicago, Illinois, United States

Site Status

Northwestern Univ Med School

Chicago, Illinois, United States

Site Status

Cook County Hosp

Chicago, Illinois, United States

Site Status

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

Univ of Minnesota

Minneapolis, Minnesota, United States

Site Status

Univ of Nebraska Med Ctr

Omaha, Nebraska, United States

Site Status

SUNY / Health Sciences Ctr at Brooklyn

Brooklyn, New York, United States

Site Status

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY / State Univ of New York

Syracuse, New York, United States

Site Status

Univ of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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

Reference Type BACKGROUND

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)

Reference Type BACKGROUND

Other Identifiers

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11170

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 194

Identifier Type: -

Identifier Source: org_study_id