Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Yale University
- Enrollment
- 458
- Locations
- 1
- Primary Endpoint
- Accuracy of sodium prediction equation in predicting suboptimal natriuretic response to a dose of diuretics
Study Overview
Brief 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:
- To develop inexpensive and efficient tools to predict diuretic response
- To understand the prevalence of therapeutically targetable mechanisms of diuretic resistance using endogenous lithium clearance
- To develop methodology to differentiate diuretic resistance mechanisms using common/inexpensive laboratory tests
- To provide proof of concept that mechanistically tailored diuretic therapy can improve natriuresis
Detailed Description
This study is a minimal-risk observational open-label single center study with randomization between two standard of care interventions. Approximately 500 patients admitted to the hospital (Yale New Haven Health System) with a clinical diagnosis of heart failure will be enrolled in the overall study.
Patients will undergo sampling of their blood and collection of urine at a minimum of 4 timepoints (called "visits"), or a minimum of 5 in the interventional arm. Patients with a low urine sodium output (<100 mmol) on Visit 1 will be eligible for 1:1 randomization to either an increased dose of their Visit 1 loop diuretic or addition of IV chlorothiazide to their Visit 1 loop diuretic.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Increased Intravenous Loop Diuretic (Bumetanide or Furosemide)
2.5x Visit 1 dose
Intervention: Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide) (Drug)
Loop Diuretic (Bumetanide or Furosemide) + IV Chlorothiazide
Loop diuretic (Bumetanide or Furosemide) dose remains the same as visit 1 dose but now with the addition of 500-1000 mg IV chlorothiazide
Intervention: IV Chlorothiazide (Drug)
Outcomes
Primary Outcomes
Accuracy of sodium prediction equation in predicting suboptimal natriuretic response to a dose of diuretics
Time Frame: 6 hours
Suboptimal Natriuretic Response is defined as a measured sodium output of \<100 mmol in the 6 hours following the dose of diuretic
Accuracy of prediction of mechanistic sub types of DR using universally available laboratory tests
Time Frame: 6 hours
The relationship between the change in fractional excretion of potassium and sodium and the change in fractional excretion of endogenous lithium will be assessed in order to develop methodology to identify the etiology of DR using universally available laboratory tests.
Prevalence of mechanistic sub types of Diuretic Resistance (DR) as defined by cutoff values of change in fractional excretion of lithium
Time Frame: 6 hours
Descriptions of the prevalence of the DR mechanisms at the different time points in the study will be reported.
Change in total 6-hour sodium output between observational and randomized intervention study days, compared between intervention groups
Time Frame: 6 hours
Sodium output in response to a dose of diuretics will be measured via urine collection.
Secondary Outcomes
- Prediction of mechanistic sub types of DR(6 hours)