Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure

Phase 1 Completed 458 enrolled Yale University National Heart, Lung, and Blood Institute (NHLBI) · collab

RandomizedParallel-groupOpen-labelDiagnostic

Summary

Effective diuresis is the primary goal of most acute decompensated heart failure hospitalizations, but diuretic resistance is common and our ability to detect it is limited. Further, there are therapeutically distinct groups of diuretic-resistant patients. These are not easily distinguished using currently available methods, leading to trial-and-error based treatment that promotes lengthy hospitalizations. The aims of this study are: 1. To develop inexpensive and efficient tools to predict diuretic response 2. To understand the prevalence of therapeutically targetable mechanisms of diuretic resistance using endogenous lithium clearance 3. To develop methodology to differentiate diuretic resistance mechanisms using common/inexpensive laboratory tests 4. To provide proof of concept that mechanistically tailored diuretic therapy can improve natriuresis

Timeline

Start: 2015-08-31
Primary completion: 2020-01-23
Completion: 2020-01-23

Outcome

Met primary endpoint

paper However, chlorothiazide addition produced a significantly larger improvement in 6-hour natriuresis (107 mmol increase [95% confidence interval (CI), 81 to 132]) PMID 40938670 ↗

Publications

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Bumetanide	Small molecule	—	Intravenous
Subject	Chlorothiazide	Small molecule	500 mg	Intravenous
Subject	Chlorothiazide	Small molecule	1000 mg	Intravenous
Subject	Furosemide	Other / unclassified	—	Intravenous