Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure
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|ClinicalTrials.gov Identifier: NCT02546583|
Recruitment Status : Active, not recruiting
First Posted : September 11, 2015
Last Update Posted : July 1, 2020
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
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure||Drug: Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide) Drug: IV Chlorothiazide||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||458 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Diagnosing and Targeting Mechanisms of Diuretic Resistance in Heart Failure|
|Actual Study Start Date :||August 31, 2015|
|Estimated Primary Completion Date :||July 31, 2023|
|Estimated Study Completion Date :||July 31, 2023|
Experimental: Increased Intravenous Loop Diuretic (Bumetanide or Furosemide)
2.5x Visit 1 dose
Drug: Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide)
An increase to 2.5x the Visit 1 dose of loop diuretic (bumetanide or furosemide).
Experimental: 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
Drug: IV Chlorothiazide
No Intervention: 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.
- 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
- 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.
- 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.
- Change in total 6-hour sodium output between observational and randomized intervention study days [ Time Frame: 6 hours ]Sodium output in response to a dose of diuretics will be measured via urine collection.
- Prediction of mechanistic sub types of DR [ Time Frame: 6 hours ]Relationship between the fractional excretion of magnesium or calcium with the fractional excretion of endogenous lithium will also be assessed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02546583
|United States, Connecticut|
|New Haven, Connecticut, United States|