Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure

Abstract

Objectives: 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).

Keywords: biomarkers; clinical trial; heart failure.

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Schematic diagram for the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in HF (GUIDE-IT) trial

GUIDE-IT aims to randomize approximately 1100 high risk chronic heart failure patients with left ventricular ejection fraction ≤ 40% to either optimized guideline recommended therapy or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP target of

Figure 2. Trial Organization

The study is being conducted under the leadership of an Executive Committee comprised of cardiologists with extensive experience caring for patients with HF that has overall responsibility for study conduct. The Duke Clinical Research Institute will house the clinical coordinating center (CCC), data coordinating center (DCC), and economics and quality of life cores are at the Duke Clinical Research Institute (DCRI).