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 - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00008866

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Biological: Tetanus Toxoid Vaccine Drug: Hydroxyurea Drug: Didanosine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Double-Blind, Safety Study
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS Medicines

Drug Information available for: Didanosine Tetanus Vaccine Hydroxyurea

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

301

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.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00008866

Locations

United States, California
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Willow Clinic
Menlo Park, California, United States, 94025
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Beth Israel Med Ctr
New York, New York, United States, 10003
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	David Asmuth
Study Chair:	Judith Feinberg
Study Chair:	Richard Pollard

More Information

Additional Information:

Click here for more information about didanosine This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	ACTG A5069, AACTG A5069, Substudy AACTG A5070s
Study First Received:	January 18, 2001
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00008866 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

HIV-1
Didanosine
Drug Therapy, Combination
Drug Administration Schedule
CD4-Positive T-Lymphocytes
Hydroxyurea

RNA, Viral
Genotype
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hydroxyurea
Hematologic Agents
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

RNA Virus Infections
Antisickling Agents
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 30, 2009