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Trial record 1 of 1 for:    NCT00867048
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Strategic Timing of Antiretroviral Treatment (START)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark
Medical Research Council
The Kirby Institute for Infection and Immunity in Society
The Institute for Clinical Research at the Veterans Affairs Medical Center -- Washington, D.C., USA
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
German Federal Ministry of Education and Research
NEAT - European AIDS Treatment Network
National Health and Medical Research Council, Australia
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Abbott
Bristol-Myers Squibb
Gilead Sciences
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00867048
First received: March 20, 2009
Last updated: October 28, 2016
Last verified: October 2016
  Purpose

Objectives:

  • To find out if the chance of developing a serious illness or of getting AIDS is less if patients start taking HIV medicines at a time when their cluster-of-differentiation-4 (CD4)+ cell count is still fairly high, instead of waiting until the CD4+ count is at the level where there is good evidence for starting medicines.
  • To learn more about how a strategy of starting HIV medicines early might affect other aspects of care, such as the chances of developing other illnesses or resistance to HIV medicines, the frequency of doctor visits, the cost of medical care, and general health and satisfaction.

Condition Intervention Phase
HIV Infection Drug: All licensed antiretroviral medications Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Strategic Timing of AntiRetroviral Treatment

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Composite endpoint of AIDS, serious non-AIDS diagnoses, and all-cause mortality [ Time Frame: 4.5 years ]

Secondary Outcome Measures:
  • Components of the composite primary outcome measure [ Time Frame: 4.5 years ]
  • Specific non-AIDS diagnoses [ Time Frame: 4.5 years ]
  • Adverse events [ Time Frame: 4.5 years ]
  • Hospitalization, health-care utilization, quality of life [ Time Frame: 4.5 years ]
  • HIV drug resistance and transmission risk behavior [ Time Frame: 4.5 years ]
  • Change in neurocognitive function (in a subset of participants) [ Time Frame: 4.5 years ]
  • Obtain a whole blood sample from which DNA will be extracted to study validated genetic variants that determine the risk of the various primary and secondary outcomes assessed in START (in a subset of participants) [ Time Frame: Blood taken at study entry and stored in a central repository indefinitely ]
  • Evaluate understanding of study information and satisfaction with the consent process among START participants, after receiving information from either a standard or a concise consent form (at a subset of sites) [ Time Frame: Before randomization into START ]
  • Large and small artery elasticity (in a subset of participants) [ Time Frame: 4.5 years ]
  • Rate of lung function decline (in a subset of participants) [ Time Frame: 4.5 years ]
  • Changes in bone mineral density (in a subset of participants) [ Time Frame: 4.5 years ]

Enrollment: 4688
Study Start Date: March 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Early ART
Initiate ART immediately following randomization
Drug: All licensed antiretroviral medications
In both arms, participants may be prescribed any licensed antiretroviral medication, in accordance with national treatment guidelines. The nature of the intervention is the timing of when to begin treatment with these medications, as described in the two treatment arms.
Active Comparator: Deferred ART
Defer ART until the CD4+ count declines to <350 cells/cu mm or AIDS develops
Drug: All licensed antiretroviral medications
In both arms, participants may be prescribed any licensed antiretroviral medication, in accordance with national treatment guidelines. The nature of the intervention is the timing of when to begin treatment with these medications, as described in the two treatment arms.

  Hide Detailed Description

Detailed Description:

Background:

  • Most guidelines agree that if the number of your CD4+ cells (cells in your blood which help fight infection) drops below 350 cells/mm3, or if you have symptoms of AIDS, you should start taking HIV medicines. There are randomized trials that support this recommendation. (Randomized trials are usually considered the strongest form of evidence to support treatment decisions. Other studies, like observational studies, provide evidence too, but the evidence is often considered to be weaker than evidence from randomized trials. A randomized trial gives the most certain information about how well a treatment works because randomization makes sure each group is similar except for the treatment they receive.) Some experts believe that HIV treatment should be started even when the number of CD4+ cells is above 350 cells/mm3. For example, guidelines issued in the US in December 2009 include a new recommendation for starting HIV medicines if your CD4+ cell count is between 350 and 500 cells/mm3. However, this recommendation is based on information from observational studies, not randomized trials. We are doing this study to find out if the chances of getting a serious illness or of getting AIDS are less if people start taking HIV medicines at a time when their CD4+ cell counts are still fairly high, instead of waiting to take HIV medicines at a CD4+ count where there is good evidence for starting medicines.

Objectives:

  • To find out if the chance of developing a serious illness or of getting AIDS is less if patients start taking HIV medicines at a time when their CD4+ cell count is still fairly high, instead of waiting until the CD4+ count is at the level where there is good evidence for starting medicines.
  • To learn more about how a strategy of starting HIV medicines early might affect other aspects of care, such as the chances of developing other illnesses or resistance to HIV medicines, the frequency of doctor visits, the cost of medical care, and general health and satisfaction.

Eligibility:

  • Patients 18 years of age and older who are infected with HIV, have CD4+ cell counts of greater than 500 cells/mm3, and who have never had antiretroviral therapy to treat HIV.

Design:

  • Initial screening visits (2) to draw blood for CD4+ cell counts and provide a full medical history
  • Patients will be randomly split into two groups:

Early: Patients will begin receiving HIV medications from the start of the study.

Deferred: Patients will begin to take HIV medications when the CD4 drops below 350 cells/mm3, or they develop AIDS or other symptoms of HIV infection.

  • HIV medications for each patient will be determined by the study doctors.
  • Evaluations during the treatment period:
  • Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
  • Questions about daily life, including sexual behaviors.
  • Blood and urine tests.
  • Heart tests with electrocardiogram.
  • Patients will return for evaluations at 1 and 4 months after randomization, and every 4 months thereafter for the duration of the study.

Substudies will take advantage of the START randomization to compare outcomes in people starting ART early vs. later.

The purpose of this randomized study is to determine whether immediate initiation of antiretroviral treatment (ART) is superior to deferral of ART until the CD4+ declines below 350 cells/mm(3) in terms of morbidity and mortality in HIV-1 (subsequently referred to as HIV) infected persons who are antiretroviral naive with a CD4+ count above 500 cells/mm(3).

The study will enroll an estimated 4,000 participants. Participants will be followed for at least 3 years after enrollment, to a common closing date.

Substudies will take advantage of the START randomization to compare outcomes in people starting ART early vs. later. These will measure outcomes that do not require the entire sample size of START to determine whether early ART is related to a difference in these outcomes over the course of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Signed informed consent
  • HIV infection documented by a plasma HIV RNA viral load, rapid HIV test or any licensed* ELISA test; and confirmed by another test using a different method including but not limited to a rapid HIV test, Western Blot, HIV culture, HIV antigen, or HIV pro-viral DNA at any time prior to study entry.
  • Age greater than or equal to 18 years
  • Karnofsky performance score greater than or equal to 80 (an indication that the participant can perform normal activities)
  • Perceived life expectancy of at least 6 months
  • For women of child-bearing potential, willingness to use contraceptives as described in the product information of the ART drugs they are prescribed
  • Two CD4+ cell counts greater than 500 cells/mm(3) at least 2 weeks apart within 60 days before randomization

    • The term licensed refers to an FDA-approved kit or, for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country. Confirmation of the initial test result must use a test method that is different than the one used for the initial assessment.

EXCLUSION CRITERIA:

  • Any previous use of ART or interleukin-2 (IL-2)
  • Diagnosis of any clinical AIDS event before randomization (including esophageal candidiasis and chronic Herpes simplex infection)
  • Presence of HIV progression such as oral thrush, unexplained weight loss, or unexplained fever
  • Cardiovascular event (myocardial infarction, angioplasty, coronary-artery bypass grafting, stroke) within 6 months before randomization
  • Non-AIDS-defining cancer, excluding basal and squamous cell skin cancer, within 6 months before randomization
  • Dialysis within 6 months before randomization
  • Diagnosis of decompensated liver disease before randomization
  • Current imprisonment, or compulsory detention (involuntary incarceration) for treatment of a psychiatric or physical illness
  • Current pregnancy or breastfeeding (a negative serum or urine pregnancy test is required within 14 days before randomization for women of child-bearing potential)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00867048

  Show 218 Study Locations
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark
Medical Research Council
The Kirby Institute for Infection and Immunity in Society
The Institute for Clinical Research at the Veterans Affairs Medical Center -- Washington, D.C., USA
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
German Federal Ministry of Education and Research
NEAT - European AIDS Treatment Network
National Health and Medical Research Council, Australia
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Abbott
Bristol-Myers Squibb
Gilead Sciences
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Tibotec Pharmaceutical Limited
Investigators
Principal Investigator: James D Neaton, PhD University of Minnesota - Clinical and Translational Science Institute
Study Chair: Abdel Babiker, PhD Medical Research Council Clinical Trials Unit, London
Study Chair: Sean Emery, PhD National Centre in HIV Epidemiology & Clinical Research, UNSW, Sydney
Study Chair: Fred Gordin, MD Veterans Affairs Medical Center -- Washington, DC
Study Chair: Jens Lundgren, MD, DMSc Copenhagen HIV Programme
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00867048     History of Changes
Obsolete Identifiers: NCT00821171
Other Study ID Numbers: 0603M83587
U01AI068641 ( US NIH Grant/Contract Award Number )
2008-006439-12 ( EudraCT Number )
Study First Received: March 20, 2009
Last Updated: October 28, 2016

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
highly active antiretroviral therapy (HAART)
CD4 Count
Early Intervention
HIV
HIV Infection
HIV Infections
treatment naive

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on June 26, 2017