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This study will evaluate whether supplementation of exogenous ketones in patients with severe left ventricular dysfunction and acutely decompensated heart failure requiring inotropic therapy would improve the patient's hemodynamics and symptoms.
The study will include patients with acutely decompensated chronic heart failure requiring inotropic therapy for the syndrome of low cardiac output. While being on the inotropic therapy, the patients will be randomized to oral supplementation of exogenous ketones vs. placebo, which will be repeatedly administered over 9 hours. The patients will undergo continuous invasive hemodynamic monitoring by pulmonary artery catheter, repeated laboratory assessment, and repeated assessment of the severity of symptoms for 24 hours.
Exogenous ketones will be administered orally using monoester 3-OHB concentrate without added salts (25g 3-OHB in 65ml H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent). The drink will be administered over 10 mins every 3 hours, 3 times in a row (hour 0, 3, 6).
All patients with K<3.7 mmol/l will receive a continuous infusion of 7.5% potassium until reach target K levels of 4.0-4.9 mmol /l. Glycemia will be controlled as needed by insulin and dextrose to maintain glucose concentration of 4 - 12 mmol/l
All patients will receive standard treatment of acute heart failure, including intravenous diuretics and inotropic therapy. The recommended inotropic therapy will include milrinone 0.5 ug/kg/min, levosimendan 0.1 ug/kg/min up to 25mg without initial bolus, or dobutamine 0.5 ug/kg/min in patients without chronic therapy with beta-blockers.
The severity of symptoms will be self-reported by the patient using 1-10 visual analog scale.
Workflow:
Statistical methods:
Each study arm will include 12 patients. The study size was estimated to have power of (1 - beta) of 0.8 and alpha of 5% for between-group comparison of changes in cardiac index and stroke volume index by ANOVA and for comparison of the changes in cardiac index and stroke volume index by paired t-tests.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Supplementation of exogenous ketones | Experimental | Exogeneous ketones will be administered orally using monoester 3-OHB concentrate without added salts (25g 3-OHB in 65ml H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent). The drink will be administered over 10 mins every 3 hours, 3 times in a row. |
|
| Control group | Placebo Comparator | The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 25g Ketone monoester without added salts | Dietary Supplement | oral supplementation of ketone monoester |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum change of stroke volume index | Maximum change of stroke volume index (ml/m2) between baseline and hour 1 - 3 | Maximum value of stroke volume index measured between hour 1 - 3 of the study protocol at 15-minute intervals |
| Maximum change of cardiac index | Maximum change of cardiac index (L/m2) between baseline and hour 1 - 3 | Maximum value of cardiac index measured between hour 1 - 3 of the study protocol at 15-minute intervals |
| Change of mean stroke volume index | Difference between baseline stroke volume index and mean stroke volume index (ml/m2) during the study protocol | Mean value of stroke volume index measured every 15 minutes during 9 hours of the study protocol |
| Change of mean cardiac index | Difference between baseline cardiac index (L/m2) and mean cardiac index during the study protocol | Mean value of cardiac index measured every 15 minutes during 9 hours of the study protocol |
| Measure | Description | Time Frame |
|---|---|---|
| Change in patient/symptoms | Change in patient-referred symptoms by visual-analog scale (1=unbearable dyspnea, 10=no symptoms) | Symptoms scored at hours 0, 1, 10, 24 and expressed as an area under the curve |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marek Sramko, MD, PhD | Contact | +420776246127 | marek.sramko@ikem.cz |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Clinical and Experimental Medicine (IKEM) | Recruiting | Prague | 14059 | Czechia |
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| ID | Term |
|---|---|
| D002303 | Cardiac Output, Low |
| D007662 | Ketosis |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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randomisation 1:1 to active treatment (exogenous ketones) vs. placebo (drinking water of equivalent volume)
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The participant and the physician in charge of the participant will be blinded to the given treatment (ketone drink vs. placebo)
| Placebo | Other | The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml) |
|
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |