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:
Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark
Medical Research Council (MRC) Clinical Trials Unit -- London, United Kingdom
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
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 9, 2014
Last verified: October 2014

March 20, 2009
October 9, 2014
March 2009
December 2015   (final data collection date for primary outcome measure)
Composite endpoint of AIDS, serious non-AIDS diagnoses, and all-cause mortality [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
To determine whether early ART is superior to deferred ART in delaying the occurrence of a composite outcome consisting of AIDS, non-AIDS, or death from any cause.
Complete list of historical versions of study NCT00867048 on ClinicalTrials.gov Archive Site
  • Components of the composite primary outcome measure [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  • Specific non-AIDS diagnoses [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  • Hospitalization, health-care utilization, quality of life [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  • HIV drug resistance and transmission risk behavior [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  • Change in neurocognitive function (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Large and small artery elasticity (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  • Rate of lung function decline (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  • Changes in bone mineral density (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
To compare early ART to deferred ART for each component of the primary composite endpoint: AIDS or death from AIDS, Non-AIDS or death not attributable to AIDS following secondary outcomes: All cause mortality, Non-AIDS, CVD, ESRD, AIDS, etc.
Not Provided
Not Provided
 
Strategic Timing of Antiretroviral Treatment
Strategic Timing of AntiRetroviral Treatment

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infection
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.
  • Experimental: Early ART
    Initiate ART immediately following randomization
    Intervention: Drug: All licensed antiretroviral medications
  • Active Comparator: Deferred ART
    Defer ART until the CD4+ count declines to <350 cells/cu mm or AIDS develops
    Intervention: Drug: All licensed antiretroviral medications

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
4688
December 2015
December 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Chile,   Czech Republic,   Denmark,   Estonia,   Finland,   France,   Germany,   Greece,   India,   Ireland,   Israel,   Italy,   Luxembourg,   Malaysia,   Mali,   Mexico,   Morocco,   Nigeria,   Norway,   Peru,   Poland,   Portugal,   Puerto Rico,   South Africa,   Spain,   Sweden,   Switzerland,   Thailand,   Uganda,   United Kingdom
 
NCT00867048
0603M83587, U01AI068641, 2008-006439-12
Yes
University of Minnesota - Clinical and Translational Science Institute
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 (MRC) Clinical Trials Unit -- London, United Kingdom
  • 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
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
University of Minnesota - Clinical and Translational Science Institute
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP