Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/26/2017 |
| Start Date: | August 2015 |
| End Date: | July 2025 |
| Contact: | Jeffrey Testani, MD |
| Email: | Jeffrey.Testani@yale.edu |
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
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
This study is a minimal-risk observational open-label single center study with randomization
between two standard of care interventions. Approximately 200 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 urine at a minimum of 4 timepoints (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.
between two standard of care interventions. Approximately 200 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 urine at a minimum of 4 timepoints (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.
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
We found this trial at
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