Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

458 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2020-01-23

Brief Summary

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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

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Detailed Description

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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.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Increased Intravenous Loop Diuretic (Bumetanide or Furosemide)

2.5x Visit 1 dose

Group Type EXPERIMENTAL

Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide)

Intervention Type DRUG

An increase to 2.5x the Visit 1 dose of loop diuretic (bumetanide or furosemide).

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

Group Type EXPERIMENTAL

IV Chlorothiazide

Intervention Type DRUG

Observational Arm

Subjects taking an IV loop diuretic (Bumetanide or Furosemide) that have sodium output greater than 100 mmol. These subjects will continue to be followed and have data collected on them.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide)

An increase to 2.5x the Visit 1 dose of loop diuretic (bumetanide or furosemide).

Intervention Type DRUG

IV Chlorothiazide

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years
* Clinical diagnosis of ADHF with at least one objective sign of volume overload: rales, edema, elevated JVP, preadmission weight gain
* Current use of bolus IV loop diuretic therapy and projected need by the treating clinician for continued treatment with IV diuretics for at least 3 days with the goal of significant fluid removal (\>1L net fluid loss/day)

* Cumulative 6-hour sodium output \< 100 mmol following Visit 1 IV loop diuretic dose
* Visit 1 IV loop diuretic dose ≤ 160 mg of furosemide equivalents
* Serum sodium \> 125 mmol/L
* At least 6 hours since last dose of diuretic

Exclusion Criteria

* Inability to perform informed consent or comply with the serial urine collection procedures
* Significant bladder dysfunction or urinary incontinence
* Hematocrit less than 21% or active bleeding

For patients in the interventional arm:

* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No