Acute Heart FailurePhase 3KADHEFNCT04698005
Exogenous Ketones for Acutely Decompensated HEart Failure
A Phase 3 study testing 25g Ketone monoester without added salts in people with Acute Heart Failure and Low Cardiac Output Syndrome, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Heart Failure, Low Cardiac Output Syndrome, Hemodynamic Instability
- What is being tested?
- 25g Ketone monoester without added salts
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteCzechia
- Study dates
- 2 Dec 2020to 31 Dec 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic heart failure due ischemic or nonischemic cardiomyopathy
- Acute decompensation of heart failure with the need of inotropes
- Achievement of relative stabilization on inotropes (INTERMACS class >2)
- Left ventricular ejection fraction <= 35%
- Age >18 years
Who cannot join
- Deteriorating cardiogenic shock with likely need of mechanical circulatory support in the subsequent 48 hours
- Chronic kidney disease grade 4 or 5
- Diabetic ketoacidosis (3-OHB >2mmol/l at baseline)
- Hemodynamic severe arrhythmias
- Acute heart failure due to transient triggers (acute coronary syndrome, atrial fibrillation, infection etc..)
- Contraindications to invasive hemodynamic monitoring
Trial locations and contacts
1 site in 1 country.
Czechia1 site, 1 recruiting
- Recruiting
Institute for Clinical and Experimental Medicine (IKEM)
Prague, 14059
Marek Sramko, MD, PhD, +420731682681, marek.sramko@ikem.cz
About this study
Official title: Exogenous Ketones for Acutely Decompensated Heart Failure
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.
Read the detailed description
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:
- Hemodynamic assessment, assessment of ketones concentration: 1-3h before randomization, 0-9h hourly, 16-24h (next morning)
- Biochemical assessment (renal function, liver enzymes, BNP, hs-TnT) 0h, 9h, 16-24h
- Assessment of symptoms and Scv02: 0h, 1h, 3h, 9h, 16-24h
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.
- Being tested
- 25g Ketone monoester without added salts, Placebo
- Medical subject headings
- Cardiac Output, Low, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
25g Ketone monoester without added saltsDietary supplement
Also called 25g 3-OHB in 65ml, H.V.M.N Ketone Ester, H.V.M.N, USA or equivalent
oral supplementation of ketone monoester
PlaceboOther
The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: 25g Ketone monoester without added salts |
| Control group | Placebo comparator | The patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum change of stroke volume index
Maximum change of stroke volume index (ml/m2) between baseline and hour 1 - 3
Measured: 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
Measured: 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
Measured: 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
Measured: Mean value of cardiac index measured every 15 minutes during 9 hours of the study protocol
Secondary outcomes (1)
Change in patient/symptoms
Change in patient-referred symptoms by visual-analog scale (1=unbearable dyspnea, 10=no symptoms)
Measured: Symptoms scored at hours 0, 1, 10, 24 and expressed as an area under the curve
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start2 Dec 2020
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomisation 1:1 to active treatment (exogenous ketones) vs. placebo (drinking water of equivalent volume)
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute for Clinical and Experimental Medicine
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Marek Sramko, Institute for Clinical and Experimental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04698005
- Sponsor's protocol ID
- A-20-28
- Acronym
- KADHEF
- Status last verified
- Jan 2021
- First submitted
- 2 Dec 2020
- Last updated
- 6 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exogenous Ketones for Acutely Decompensated Heart Failure
- ClinicalTrials.gov ID
- NCT04698005
- Acronym / sponsor ID
- KADHEF / A-20-28
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Institute for Clinical and Experimental MedicineOther government
- Study start
- 2 Dec 2020 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Hemodynamic assessment, assessment of ketones concentration: 1-3h before randomization, 0-9h hourly, 16-24h (next morning)
- Biochemical assessment (renal function, liver enzymes, BNP, hs-TnT) 0h, 9h, 16-24h
- Assessment of symptoms and Scv02: 0h, 1h, 3h, 9h, 16-24h
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- randomisation 1:1 to active treatment (exogenous ketones) vs. placebo (drinking water of equivalent volume)
| Arm | Type | Receives |
|---|---|---|
| Supplementation of exogenous ketones | Experimental | Dietary Supplement: 25g Ketone monoester without added saltsExogeneous 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 | Other: PlaceboThe patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Chronic heart failure due ischemic or nonischemic cardiomyopathy
- Acute decompensation of heart failure with the need of inotropes
- Achievement of relative stabilization on inotropes (INTERMACS class >2)
- Left ventricular ejection fraction <= 35%
- Age >18 years
Key exclusion criteria (6 listed)
- Deteriorating cardiogenic shock with likely need of mechanical circulatory support in the subsequent 48 hours
- Chronic kidney disease grade 4 or 5
- Diabetic ketoacidosis (3-OHB >2mmol/l at baseline)
- Hemodynamic severe arrhythmias
- Acute heart failure due to transient triggers (acute coronary syndrome, atrial fibrillation, infection etc..)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 25g Ketone monoester without added saltsAlso: 25g 3-OHB in 65ml, H.V.M.N Ketone Ester, H.V.M.N, USA or equivalentoral supplementation of ketone monoester | Dietary supplement | Supplementation of exogenous ketones |
| PlaceboThe patients will receive a placebo drink (drinking water) of equivalent volume (3x 65ml) | Other | Control group |
Primary outcome
Maximum change of stroke volume index
Time frame: Maximum value of stroke volume index measured between hour 1 - 3 of the study protocol at 15-minute intervals
Maximum change of stroke volume index (ml/m2) between baseline and hour 1 - 3
Maximum change of cardiac index
Time frame: Maximum value of cardiac index measured between hour 1 - 3 of the study protocol at 15-minute intervals
Maximum change of cardiac index (L/m2) between baseline and hour 1 - 3
Change of mean stroke volume index
Time frame: Mean value of stroke volume index measured every 15 minutes during 9 hours of the study protocol
Difference between baseline stroke volume index and mean stroke volume index (ml/m2) during the study protocol
Change of mean cardiac index
Time frame: Mean value of cardiac index measured every 15 minutes during 9 hours of the study protocol
Difference between baseline cardiac index (L/m2) and mean cardiac index during the study protocol
1 secondary outcome
Change in patient/symptoms
Time frame: Symptoms scored at hours 0, 1, 10, 24 and expressed as an area under the curve
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
- Individual participant dataSharing planned: Undecided
Related trials for Acute Heart Failure
Not yet recruiting
Routine Magnesium Testing and Supplementation in Acute Heart Failure (MAG-HF)
Acute Heart Failure (AHF)
RecruitingPhase 3
Optimal Diuretic Therapies for Acute Heart Failure With Volume Overload
Acute Heart Failure
Recruiting
Evaluation of Fibroscan® Performance in Diagnosing Acute Heart Failure in Patients Presenting to the Emergency Department
Acute Heart Failure (AHF)
RecruitingObservational study
Cardiogenic Shock Working Group Registry
Cardiogenic Shock
RecruitingObservational study
Changes in Skeletal Muscle Thickness in Patients With Acute Heart Failure
Heart Failure, Muscle Atrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 25g Ketone monoester without added salts in people with Acute Heart Failure and Low Cardiac Output Syndrome, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marek Sramko, MD, PhD (+420776246127, marek.sramko@ikem.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum change of stroke volume index (time frame: Maximum value of stroke volume index measured between hour 1 - 3 of the study protocol at 15-minute intervals). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2021.