A Phase 1 interventional study of Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide) and IV Chlorothiazide in Heart Failure, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-17.
Sponsored by Yale University · Phase 1, Interventional, and Diagnostic
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:
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.
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's enrollment of 458 is above the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
For all patients:
Inclusion criteria:
Exclusion criteria:
For patients in the interventional arm:
Inclusion criteria:
Exclusion criteria:
2.5x Visit 1 dose
Drug: Increased Intravenous Bolus Loop Diuretic Dose (Bumetanide or Furosemide)
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
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.
An increase to 2.5x the Visit 1 dose of loop diuretic (bumetanide or furosemide).
Accuracy of sodium prediction equation in predicting suboptimal natriuretic response to a dose of diuretics
Suboptimal Natriuretic Response is defined as a measured sodium output of \<100 mmol in the 6 hours following the dose of diuretic
Time frame: 6 hours
Prevalence of mechanistic sub types of Diuretic Resistance (DR) as defined by cutoff values of change in fractional excretion of lithium
Descriptions of the prevalence of the DR mechanisms at the different time points in the study will be reported.
Time frame: 6 hours
Accuracy of prediction of mechanistic sub types of DR using universally available laboratory tests
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.
Time frame: 6 hours
Change in total 6-hour sodium output between observational and randomized intervention study days, compared between intervention groups
Sodium output in response to a dose of diuretics will be measured via urine collection.
Time frame: 6 hours
Prediction of mechanistic sub types of DR
Relationship between the fractional excretion of magnesium or calcium with the fractional excretion of endogenous lithium will also be assessed
Time frame: 6 hours
This study is completed, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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