Trial DesignDesign of the RELAXin in Acute Heart Failure Study
Section snippets
Background
Acute heart failure (AHF) remains a major public health burden with a high prevalence and a poor prognosis. More than 80% of patients who present to the hospital with AHF complain of dyspnea.1 Despite the importance of symptom relief to patients,2 dyspnea is not relieved substantially in about 50% of patients after 24 hours of therapy and in 25% of patients at discharge.3, 4, 5 Thus, faster and more complete symptom resolution is an important goal in the development of new AHF therapies.6, 7
Pre-RELAX-AHF: the phase 2 study
Pre-RELAX-AHF and RELAX-AHF-1 are described in a single phase 2/3 protocol. The Pre-RELAX-AHF26 was a phase 2, placebo-controlled, double-blind, parallel-group, dose-finding study conducted in 234 patients with AHF, dyspnea, congestion on chest radiograph, elevated natriuretic peptides, mild-to-moderate renal dysfunction, and SBP >125 mm Hg. Patients were randomized within 16 hours of presentation to up to 48 hours of continuous IV infusion of placebo or 10, 30, 100, or 250 μg/kg per day RLX030
Discussion
In Pre-RELAX-AHF, 30 μg/kg per day RLX030 was associated with an increased proportion of patients with dyspnea relief in the first 24 hours, using the Likert scale, and with decreased severity of dyspnea through day 5, using the VAS AUC, compared with placebo.26 Patients treated with RLX030 also tended to have a shorter average hospital stay, more days alive and out of the hospital, lower 60-day risks of CV death or rehospitalization and all-cause death or rehospitalization, and lower 180-day
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Site enrollment rate, outcomes, and study drug effects in a multicenter trial. Results from RELAX-AHF
2018, International Journal of CardiologyA systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure
2018, International Journal of CardiologyKidney in Heart Failure
2017, Encyclopedia of Cardiovascular Research and MedicineDevelopment and validation of a risk model for in-hospital worsening heart failure from the Acute Decompensated Heart Failure National Registry (ADHERE)
2016, American Heart JournalCitation Excerpt :We may have had different findings if we developed a model that considered other similar outcomes such as death or discharge with early readmission. Finally, although the model has good internal validity, we were unable to validate the risk model outside of ADHERE using a consistent definition of in-hospital worsening heart failure because of the different ways worsening heart failure was defined in various data sets.6-10,32-35 The ADHERE worsening heart failure risk model is a clinical tool with good calibration and discrimination for use in hospitalized patients with acute heart failure to identify patients at risk for in-hospital worsening heart failure.
RCT reg number NCT00520806
David Hasdai, MD, served as guest editor for this article.