Strategic Timing of Antiretroviral Treatment - Full Text View

Strategic Timing of Antiretroviral Treatment (START)

This study is currently recruiting participants.

Verified April 2012 by University of Minnesota - Clinical and Translational Science Institute

First Received on March 20, 2009. Last Updated on April 9, 2012 History of Changes

Sponsor:	University of Minnesota - Clinical and Translational Science Institute
Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark Medical Research Council (MRC) Clinical Trials Unit -- London, United Kingdom Kirby Institute 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 Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:	NCT00867048

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 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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Strategic Timing of AntiRetroviral Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	4000
Study Start Date:	March 2009
Estimated Study Completion Date:	March 2015
Estimated Primary Completion Date:	March 2015 (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.

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Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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 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

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

Show 226 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 (MRC) Clinical Trials Unit -- London, United Kingdom

Kirby Institute

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

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:

INSIGHT network website, including information on the START trial This link exits the ClinicalTrials.gov site

Publications:

Egger M, May M, Chêne G, Phillips AN, Ledergerber B, Dabis F, Costagliola D, D'Arminio Monforte A, de Wolf F, Reiss P, Lundgren JD, Justice AC, Staszewski S, Leport C, Hogg RS, Sabin CA, Gill MJ, Salzberger B, Sterne JA; ART Cohort Collaboration. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet. 2002 Jul 13;360(9327):119-29. Erratum in: Lancet 2002 Oct 12;360(9340):1178.

May M, Sterne JA, Sabin C, Costagliola D, Justice AC, Thiébaut R, Gill J, Phillips A, Reiss P, Hogg R, Ledergerber B, D'Arminio Monforte A, Schmeisser N, Staszewski S, Egger M; Antiretroviral Therapy (ART) Cohort Collaboration. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies. AIDS. 2007 May 31;21(9):1185-97.

Silverberg MJ, Neuhaus J, Bower M, Gey D, Hatzakis A, Henry K, Hidalgo J, Lourtau L, Neaton JD, Tambussi G, Abrams DI. Risk of cancers during interrupted antiretroviral therapy in the SMART study. AIDS. 2007 Sep 12;21(14):1957-63.

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

Kunisaki KM, Quick H, Baker JV. HIV antiretroviral therapy reduces circulating surfactant protein-D levels. HIV Med. 2011 Oct;12(9):580-1. No abstract available.

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, 2008-006439-12
Study First Received:	March 20, 2009
Last Updated:	April 9, 2012
Health Authority:	Argentina: Ministry of Health Australia: National Health and Medical Research Council Belgium: Institutional Review Board Brazil: Ethics Committee Chile: Instituto de Salud Publica de Chile Denmark: Ethics Committee European Union: European Medicines Agency Finland: Ethics Committee France: National Consultative Ethics Committee for Health and Life Sciences Germany: Ethics Commission Greece: Ethics Committee Israel: Ethics Commission Italy: National Bioethics Committee Mali: Ministry of Health Morocco: Ministry of Public Health Peru: Ethics Committee Poland: Ethics Committee Singapore: Domain Specific Review Boards South Africa: National Health Research Ethics Council Spain: Ethics Committee Switzerland: Ethikkommission Thailand: Ethical Committee United Kingdom: Research Ethics Committee United States: Federal Government United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:

HAART
CD4 Count
Early Intervention
HIV

HIV Infection
HIV Infections
treatment naive

Additional relevant MeSH terms:

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 May 23, 2012