Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure

Trial Purpose and Description

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

Ages: 18 years and older

Gender: Both

Eligibility Criteria

Inclusion Criteria:

For all patients:

  • Clinical diagnosis of ADHF with at least one objective sign of volume overload (rales, edema, elevated JVP, or preadmission weight gain)
  • For patients in the interventional arm:
  • A projected need by the treating physician for continued treatment with IV diuretics for at least 3 days with the goal of significant fluid removal (>1L net fluid loss/day)
  • Production of < 100 mmol of sodium output on Visit 1 of the study
  • Serum sodium > 125 mmol/L
  • Study Visit 1 loop diuretic dose ≤ 160 mg of furosemide equivalents
  • At least 6 hours since last dose of diuretic

Exclusion Criteria:

  • Significant bladder dysfunction or urinary incontinence
  • Inability to comply with the serial urine collection procedures or return for the 5-7 day post discharge study visit
  • Current use or projected future requirement by the treating physician for thiazide diuretics
  • Use of high dose mineralocorticoid receptor antagonist therapy (>50mg of spironolactone or >100mg of eplerenone) or amiloride

National Heart, Lung, and Blood Institute

Start Date: 08/24/2015

End Date: 07/01/2025

Last Updated: 02/22/2018

Study HIC#: 1505015805

Get Involved

For more information about this study, contact:
Jennifer Tainsh

If you would prefer to contact a member of the Help us Discover team about this trial and other similar trials, please email helpusdiscover@yale.edu or call 1-877-978-8348.

Trial Image


Jeffrey Testani

Principal Investigator