title: Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.
abstract: OBJECTIVE
  The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of <1,000 pg/ml compared with usual care in high-risk patients with systolic heart failure (HF).
  
  
  BACKGROUND
  Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF.
  
  
  METHODS
  GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of <1,000 pg/ml. Patients in either arm of the study are followed up at regular intervals and after treatment adjustments for a minimum of 12 months. The primary endpoint of the study is time to cardiovascular death or first hospitalization for HF. Secondary endpoints include time to cardiovascular death and all-cause mortality, cumulative mortality, health-related quality of life, resource use, cost-effectiveness, and safety.
  
  
  CONCLUSIONS
  The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840).
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Electronic address: michael.felker@duke.edu.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Lawton S
authors.initials: LS
authors.lastname: Cooper
authors.affiliation: Division of Cardiology, University of Alberta, Alberta, Canada.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Ezekowitz
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Division of Cardiology, Stanford University, Palo Alto, California.
authors.forename: Nancy
authors.initials: N
authors.lastname: Houston-Miller
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Leifer
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mark
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Patrice
authors.initials: P
authors.lastname: Desvigne-Nickens
authors.affiliation: Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Gayle
authors.initials: G
authors.lastname: Paynter
authors.affiliation: Division of Cardiology, Montefiore-Einstein Medical Center, Bronx, New York.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.affiliation: Division of Cardiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy; D019317:Evidence-Based Medicine; D005081:Exercise Therapy; D054143:Heart Failure, Systolic / Q000097:blood / Q000401:mortality / Q000628:therapy*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010347:Patient Care Planning; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: biomarkers; clinical trial; heart failure