Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT)
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Open BioLINCC Study See bottom of this webpage for request information
December 2012 – September 2016
July 31, 2019
Clinical Trial URLs
Primary Publication URLs
Commercial Use Data Restrictions No
Data Restrictions Based On Area Of Research No
To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-pro-BNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with heart failure (HF) and reduced ejection fraction (HFrEF).
Heart failure is a common disorder. Standard treatment for HF include diuretics to control fluid, as well as, drugs called "neurohormonal antagonists" (such as beta-blockers and ACE-inhibitors) that help the heart work more efficiently. The natriuretic peptides, specifically amino-terminal pro–B-type natriuretic peptide (NT-pro-BNP), are biomarkers that reflect HF severity and are significantly associated with adverse outcomes in HF. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels (“guided therapy”) with inconsistent results.
Eligible participants were adults with high-risk HF, as characterized by a low ejection fraction (40% or less, median 25%), significantly elevated NT-pro-BNP (greater than 2,000 pg/mL, median 2,653 pg/mL) or BNP (greater than 400 pg/mL) within 30 days prior to enrollment, and a history of prior HF hospitalization (or equivalent) in the past year. A total of 894 patients were enrolled at 45 sites in the United States and Canada, with 446 randomized to the NT-pro-BNP-guided strategy treatment group and 448 randomized to the usual care treatment group.
GUIDE-IT was a multicenter randomized clinical trial with patients randomized to either the NT-pro-BNP-guided therapy strategy or usual care. Given the nature of the study intervention, treatment assignment was not blinded. For patients randomized to the NT-pro-BNP-guided strategy, clinicians were instructed to titrate HF therapy to target an NT-pro-BNP level <1,000 pg/mL. Specific adjustments of therapy for individual patients were at the discretion of the treating physician, but sites were encouraged to prioritize titration of neurohormonal antagonists over diuretics unless there was clinical evidence of congestion or volume overload. For patients in either group, investigators were provided with the most recent American Heart Association (AHA)/American College of Cardiology (ACC) practice guidelines for the management of HF and specific information on target doses of proven medical therapies.
After an initial visit at 2 and 6 weeks, visits occurred every 3 months throughout the remainder of the study. After therapy adjustment for HF (whether driven by NT-pro-BNP levels or clinical reasons), patients had a 2-week follow-up visit for reassessment. All patients in either group also had blinded NT-pro-BNP concentrations measured in a core laboratory at each study visit.
The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events.
The guided strategy intervention was stopped in July of 2016 (median follow-up of 15 months) after the study met prespecified inefficacy criteria. Compared to usual care, a strategy of NT-pro-BNP-guided therapy was not more effective in improving time-to-first HF hospitalization or cardiovascular mortality in high-risk patients with HFrEF.
Felker GM, Anstrom KJ, Adams KF, et al. Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA. 2017;318(8):713–720. doi:10.1001/jama.2017.10565
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Resources AvailableStudy Datasets Only
- Data Dictionary (PDF - 1.3 MB)
- GUIDE IT Annotated Forms (PDF - 14.5 MB)
- GUIDE IT Manual of Operations (PDF - 6.1 MB)
- GUIDE IT Protocol (PDF - 613.4 KB)
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