A Phase II, Double-Blind, Randomized Study to Determine the Effect of Adding Delayed Versus Immediate Hydroxyurea to a Genotypic Based, ddI-Containing, Three-Drug Antiretroviral Regimen on the Recovery of Total CD4+ T-Cell Counts and Suppression of Plasma Viral Load in Advanced HIV-1 Infected Subjects Failing a First or Second Triple Combination Therapy
Effectiveness of Early or Delayed Addition of Hydroxyurea to a Three-Drug Anti-HIV Drug Combination Including Didanosine, in Advanced HIV Patients Who Failed a First or Second Anti-HIV Triple-Drug Therapy
Sponsors
Source
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary
The purpose of this study is to find out whether or not the addition of hydroxyurea to
didanosine (ddI) and other anti-HIV medications will result in better control of HIV
infection.
The Food and Drug Administration (FDA) has approved ddI for treating HIV infections.
Hydroxyurea is approved for treating some cancers and blood disorders. It works against HIV-1
when combined with ddI. Researchers need to look at how well patients may respond to
hydroxyurea in combination with ddI and other anti-HIV drugs, and at any side effects.
Detailed Description
Increasing frequency of treatment failures on potent antiretroviral therapy has accelerated
the need for new classes of agents. Hydroxyurea, an agent broadly used for its antineoplastic
properties, has been shown to inhibit HIV-1 in vitro and in vivo when combined with the
nucleoside analogue reverse transcriptase inhibitor didanosine (ddI). There is an urgent need
to prospectively test the safety, tolerability, and efficacy of hydroxyurea in late-stage,
treatment-experienced patients.
Patients undergo genotypic analysis after registration to Step 1. Genotypic antiretroviral
resistance test (GART) along with a patient's antiretroviral drug history will be used to
select an optimal antiretroviral drug regimen (non-study drugs) for each patient. Patients
willing to initiate the GART-based regimen are randomized at Week 5 into Step 2. They are
stratified, first by level of ddI resistance, then within each strata by CD4+ T cell count,
and then assigned to 1 of 3 treatment arms to start all study drugs (ddI and hydroxyurea) and
non-study antiretroviral drugs on the day of randomization. Patients in Arm A receive ddI and
hydroxyurea placebo; Arm B, ddI and hydroxyurea placebo that is replaced by hydroxyurea after
8 weeks; and Arm C, ddI and hydroxyurea. Patients receive treatment for 48 weeks. Patients
are checked regularly for immunologic, virologic, and metabolic parameters. Patients may
elect to participate in substudy A5070s, which explores the effects of study treatment on T
cell populations and other immunologic evaluations.
Overall Status
Withdrawn
Start Date
N/A
Completion Date
N/A
Primary Completion Date
N/A
Phase
Phase 2
Study Type
Interventional
Condition
Intervention
Eligibility
Criteria
Inclusion Criteria
Patients may be eligible for this study if they:
- Are at least 13 years old.
- Have the signed consent of parent/guardian if under 18 years of age.
- Are HIV-positive.
- Have failed 1 or 2 anti-HIV drug combination therapies which had at least 3 anti-HIV
drugs each.
- Have been on stable, triple anti-HIV drug therapy for at least 16 weeks prior to study
entry.
- Have a CD4 count under 300 cells/mm3 within 45 days prior to study entry.
- Agree not to become pregnant or make anyone else pregnant while on study drugs and for
60 days after stopping drugs.
- Agree to use 2 methods of birth control while on study drugs and for 60 days after
stopping study drugs.
- Have a negative pregnancy test within 14 days prior to study entry.
Exclusion Criteria
Patients will not be eligible for this study if they:
- Received treatment for a serious infection or illness that was completed less than 2
weeks prior to study entry or, if they are still receiving treatment, he/she must have
been clinically stable for at least 14 days prior to study entry.
- Are pregnant or breast-feeding.
- Are using any drugs that affect the immune system, other than those specified by the
study.
- Received an immunization within 30 days prior to study entry.
- Have had pancreatitis.
- Have severe neuropathy (a condition affecting the nervous system).
- Received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage
colony-stimulating factor (GM-CSF) within 14 days prior to study entry.
- Abuse alcohol or drugs.
- Have any medical condition that would make the patient unable to complete the study.
- Have used hydroxyurea within 24 weeks prior to study entry.
- Had hepatitis within 60 days of study entry.
Gender
All
Minimum Age
13 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
|
David Asmuth |
Study Chair |
|
Judith Feinberg |
Study Chair |
|
Richard Pollard |
Study Chair |
Verification Date
2012-05-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
10905
ACTG A5069
AACTG A5069
Substudy AACTG A5070s
Intervention Browse
Mesh Term
Didanosine
Hydroxyurea
Firstreceived Results Date
N/A
Removed Countries
Country
United States
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Treatment
Masking
Double
Study First Submitted
January 18, 2001
Study First Submitted Qc
August 30, 2001
Study First Posted
August 31, 2001
Last Update Submitted
May 17, 2012
Last Update Submitted Qc
May 17, 2012
Last Update Posted
May 18, 2012
ClinicalTrials.gov processed this data on December 13, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.