Heart FailurePhase 2ICARDNCT05420285
Cardiometabolic Effects of Dapagliflozin in Heart Failure With Reduced or Mildly Reduced Ejection Fraction
A Phase 2 study testing Dapagliflozin in people with Heart Failure and Reduced Ejection Fraction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Gliflozins have demonstrated a beneficial effect in terms of incident heart failure and related events in patients with or without diabetes. The clinical trial ICARD is an exploratory study that aims to evaluate the cardiometabolic mechanistic effects on the myocardium of dapagliflozin in heart failure with reduced… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Heart Failure, Reduced Ejection Fraction
- What is being tested?
- Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 26 Jun 2022to May 2024
- Phase
- Phase 2
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- NYHA functional class II-IV.
- Previous hospitalization for heart failure anytime or NT-proBNP >125 pg/ml in the previous 12 months
- Left ventricular ejection fraction ≤ 50% measured at least 1 time in transthoracic echocardiography in the last 12 months
- Treated by optimal medical therapy (ACE-I or angiotensin receptor blocker or sacubitril-valsartan, and betablockers, and mineralocorticoid receptor antagonist and furosemide) unless such use was contraindicated or previously associated with side-effects leading to drug discontinuation. No change in drugs dosages in the last month.
- Able to give written informed consent
Show all 9Show fewer
- If female of childbearing potential, have a negative serum pregnancy test
- Use of a validated method of birth control until the end of the study (men and women)
- Affiliation to a social security regime
Who cannot join
- Hypersensitivity to dapagliflozin or to any of the excipients
- Current treatment with gliflozine
- Cardiac rhythm disorder including atrial fibrillation > 100 bpm
- Significant valvular heart disease including mitral or aortic regurgitation > II/IV
- Hospitalisation for heart failure or unplanned visit for worsening heart failure in the last month
- Recent (last 3 months) or planned coronary revascularization
Show all 20Show fewer
- Acute coronary syndrome, stroke, or transient ischemic attack in the last 3 months
- Body mass-index > 40 kg/m2
- Uncontrolled type 2 diabetes (Hb1AC > 9%) or type 1 diabetes
- Genetic diabetes (Maturity Onset Diabetes of the Young, MODY)
- Current treatment for cancer, cardiotoxic cancer treatment in the last year
- Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones in the last 6 weeks
- Active infectious diseases
- Hypovolemia or dehydration, severe hypokalaemia, or severe hyponatremia
- Contraindication to MRI or to contrast agents used
- Estimated glomerular filtration rate (eGFR) < 30 ml per minute per 1.73 m2 of body-surface area (according to the Modification of Diet in Renal Disease criteria)
- Patient on AME (state medical aid)
- Pregnant or breast-feeding female
- Current participation in another interventional study or being in the exclusion period at the end of a previous study
- Patient protected by law (guardianship, tutelage measure, deprived of liberty)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Pitié-Salpêtrière Hospital
Paris, 75013
Alban REDHEUIL, MD PhD, +33(0)1.42.16.55.45, alban.redheuil@aphp.fr
About this study
Official title: Cardiometabolic Effects of Dapagliflozin in Heart Failure With Reduced or Mildly Reduced Ejection Fraction: an Exploratory Study
Gliflozins have demonstrated a beneficial effect in terms of incident heart failure and related events in patients with or without diabetes. The clinical trial ICARD is an exploratory study that aims to evaluate the cardiometabolic mechanistic effects on the myocardium of dapagliflozin in heart failure with reduced ejection fraction. Deep phenotyping of cardiac and vascular function will be performed using MRI. Myocardial tissue characterization will be based on MRI and FDG-PET for glucose metabolism assessment. Liver steatosis and fibrosis will simultaneously be assessed.
Read the detailed description
Open-label, non-controlled clinical trial (Jardé 1) to assess the cardiovascular and metabolic effects of once-daily dapagliflozin 10 mg during 6 months in patients with heart failure and reduced ejection fraction.
Eligibility of patients addressed to the Department of Cardiology (Prof R. Isnard, Pitié-Salpêtrière Hospital, Paris, France) will be investigated at V0: inclusion and exclusion criteria will be checked and informed consent will be signed.
Up to twenty one days after V0, patients will come to the VMRI visit (VMRI) for the cardiac and liver gadolinium-injected MRI and AGE Reader (VRMI) and to the baseline visit (V1). Pregnancy will be ruled out in women of childbearing potential with blood beta-HCG. A blood test (including metabolomics and lipidomics) and FDG-PET MRI including Glucose Tolerance Test (GTT) will be performed. Dapagliflozin 10 mg once daily during six months will be prescribed.
Fifteen to twenty-one days after treatment initiation, a safety visit (V2) will take place in order to verify the tolerance.
A pre-final visit (V3) will be organized after a total of 23 weeks (± 1 week) of treatment. Pregnancy will be ruled out in women of childbearing potential with blood beta-HCG. A blood test (including metabolomics and lipidomics), ECG, trans-thoracic echocardiography (TTE), cardiac and liver MRI and AGE Reader will be performed.
After 24 weeks of treatment (6-month treatment), patients will come to the end of study visit (V4), to undergo the final FDG-PET MRI including Glucose Tolerance Test (GTT).
- Conditions
- Heart Failure, Reduced Ejection Fraction
- Being tested
- Dapagliflozin
- Keywords
- heart failure, HFrEF, myocardial function, fibrosis, metabolism
- Medical subject headings
- Heart Failure, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Forxiga
Dapagliflozin (Forxiga) is a very potent selective and reversible inhibitor of SGLT2.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Experimental | Dapagliflozin is taken orally, once daily at the dosage of 10 mg during 6 months. Receives: Drug: Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate changes in left ventricular (LV) extracellular mass index (ECMi) measured by MRI, induced by once-daily dapagliflozin 10mg during 6 months in patients with heart failure and reduced ejection fraction
MRI measurement of changes in left ventricular extracellular mass index (ECMI) after a 6-month once-daily dapagliflozin 10 mg regimen
Measured: 6 months
Secondary outcomes (29)
To evaluate myocardial morphology
MRI measurement of change: Left and right ventricular volumes and Left atrial volumes
Measured: 6 months
To evaluate myocardial morphology
MRI measurement of change: LV mass
Measured: 6 months
Left ventricular ejection fraction as a biomarker of myocardial function
MRI measurement of change of left ventricular ejection fraction
Measured: 6 months
Right ventricular ejection fraction as a biomarker of myocardial function
MRI measurement of change of right ventricular ejection fraction
Measured: 6 months
Left atrial ejection fraction as a biomarker of myocardial function
MRI measurement of change of left atrial ejection fraction
Measured: 6 months
Peak global longitudinal strain as a biomarker of myocardial function
MRI measurement of change of peak global LV longitudinal strain
Measured: 6 months
Peak radial strain as a biomarker of myocardial function
MRI measurement of change of peak radial LV strain
Measured: 6 months
Peak circumferential strain as a biomarker of myocardial function
MRI measurement of change of peak circumferential LV strain
Measured: 6 months
Peak circumferential strain as a biomarker of left atrial function
MRI measurement of change of peak circumferential LA strain (reservoir)
Measured: 6 months
Peak circumferential strain as a biomarker of left atrial function
MRI measurement of change of peak circumferential LA strain (booster)
Measured: 6 months
LV myocardial dense fibrosis (late gadolinium enhancement) as a biomarker of fibrosis
MRI measurement of change of LV myocardial dense fibrosis (late gadolinium enhancement mass)
Measured: 6 months
Intracellular mass index (ICMi) as a biomarker of fibrosis
MRI measurement of change of intracellular mass index (ICMi)
Measured: 6 months
Extracellular mass index (ECMi) as a biomarker of fibrosis
MRI measurement of change of extracellular mass index (ECMi)
Measured: 6 months
To evaluate adipose tissue
MRI measurement of change: epicardial adipose tissue (EAT) and steatosis (triglyceride fraction)
Measured: 6 months
To evaluate myocardial steatosis
1H-MR spectromscopy measurement of modifications of relative myocardial triglyceride content.
Measured: 6 months
To evaluate glucose metabolism
18FDG-PET-MRI measurement of change with glucose uptake analysis
Measured: 6 months
Effects of dapagliflozin therapy on the proximal aorta
High resolution cine aortic MRI measurement of ascending aortic areas
Measured: 6 months
Effects of dapagliflozin therapy on the proximal aorta
High resolution cine aortic MRI measurement of descending aortic areas
Measured: 6 months
Effects of dapagliflozin therapy on the proximal aorta
High resolution cine aortic MRI measurement of ascending aortic distensibility
Measured: 6 months
Effects of dapagliflozin therapy on the proximal aorta
High resolution cine aortic MRI measurement of descending aortic distensibility
Measured: 6 months
Effects of dapagliflozin therapy on the proximal aorta
High resolution cine aortic MRI measurement of aortic arch pulse wave velocity (PWV)
Measured: 6 months
To evaluate the evolution of body composition in multimodality imaging
MRI measurement of change in abdominal subcutaneous and visceral fat using the ATQUA method on DIXON MRI images
Measured: 6 months
To evaluate the changes in fasting glucagon
Blood measurement change in glucagon
Measured: 6 months
To evaluate the changes in fasting β-hydroxybutyrate
Blood measurement change in β-hydroxybutyrate
Measured: 6 months
To evaluate the changes in fasting glycerol
Blood measurement change in glycerol
Measured: 6 months
To evaluate the changes in free fatty acid (FFA)
Blood measurement change in free fatty acid (FFA)
Measured: 6 months
To evaluate the changes in fasting glycemia
Blood measurement change in glycemia
Measured: 6 months
To evaluate the subcutaneous tissue Advanced end-Glycation Products (AGE)
Measurement of the value of AGE on AGE reader
Measured: 6 months
Evaluation of pathophysiological changes at the molecular level (metabolite profiling)
Blood measurement of targeted metabolites by LC-MS (Liquid chromatography coupled to mass spectrometry) and by GC-MS (Gas chromatography coupled to mass spectrometry)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2022
- Study start26 Jun 2022
- Primary completionSep 2023 (estimated)
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alban REDHEUIL, MD PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05420285
- Sponsor's protocol ID
- APHP210166
- Other IDs
- 2021-000481-14
- Acronym
- ICARD
- Status last verified
- Feb 2022
- First submitted
- 12 May 2022
- Last updated
- 9 Dec 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission Nationale de l'Informatique et des Libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiometabolic Effects of Dapagliflozin in Heart Failure With Reduced or Mildly Reduced Ejection Fraction: an Exploratory Study
- ClinicalTrials.gov ID
- NCT05420285
- Acronym / sponsor ID
- ICARD / APHP210166
- Conditions
- Heart Failure, Reduced Ejection Fraction
- Keywords
- heart failure, HFrEF, myocardial function, fibrosis, metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 26 Jun 2022 (actual)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- May 2024 (estimated)
- First posted
- 15 Jun 2022 (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.
Gliflozins have demonstrated a beneficial effect in terms of incident heart failure and related events in patients with or without diabetes. The clinical trial ICARD is an exploratory study that aims to evaluate the cardiometabolic mechanistic effects on the myocardium of dapagliflozin in heart failure with reduced ejection fraction. Deep phenotyping of cardiac and vascular function will be performed using MRI. Myocardial tissue characterization will be based on MRI and FDG-PET for glucose metabolism assessment. Liver steatosis and fibrosis will simultaneously be assessed.
Detailed description
Open-label, non-controlled clinical trial (Jardé 1) to assess the cardiovascular and metabolic effects of once-daily dapagliflozin 10 mg during 6 months in patients with heart failure and reduced ejection fraction.
Eligibility of patients addressed to the Department of Cardiology (Prof R. Isnard, Pitié-Salpêtrière Hospital, Paris, France) will be investigated at V0: inclusion and exclusion criteria will be checked and informed consent will be signed.
Up to twenty one days after V0, patients will come to the VMRI visit (VMRI) for the cardiac and liver gadolinium-injected MRI and AGE Reader (VRMI) and to the baseline visit (V1). Pregnancy will be ruled out in women of childbearing potential with blood beta-HCG. A blood test (including metabolomics and lipidomics) and FDG-PET MRI including Glucose Tolerance Test (GTT) will be performed. Dapagliflozin 10 mg once daily during six months will be prescribed.
Fifteen to twenty-one days after treatment initiation, a safety visit (V2) will take place in order to verify the tolerance.
A pre-final visit (V3) will be organized after a total of 23 weeks (± 1 week) of treatment. Pregnancy will be ruled out in women of childbearing potential with blood beta-HCG. A blood test (including metabolomics and lipidomics), ECG, trans-thoracic echocardiography (TTE), cardiac and liver MRI and AGE Reader will be performed.
After 24 weeks of treatment (6-month treatment), patients will come to the end of study visit (V4), to undergo the final FDG-PET MRI including Glucose Tolerance Test (GTT).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Experimental | Drug: DapagliflozinDapagliflozin is taken orally, once daily at the dosage of 10 mg during 6 months. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years
- NYHA functional class II-IV.
- Previous hospitalization for heart failure anytime or NT-proBNP >125 pg/ml in the previous 12 months
- Left ventricular ejection fraction ≤ 50% measured at least 1 time in transthoracic echocardiography in the last 12 months
- Treated by optimal medical therapy (ACE-I or angiotensin receptor blocker or sacubitril-valsartan, and betablockers, and mineralocorticoid receptor antagonist and furosemide) unless such use was contraindicated or previously associated with side-effects leading to drug discontinuation. No change in drugs dosages in the last month.
Key exclusion criteria (20 listed)
- Hypersensitivity to dapagliflozin or to any of the excipients
- Current treatment with gliflozine
- Cardiac rhythm disorder including atrial fibrillation > 100 bpm
- Significant valvular heart disease including mitral or aortic regurgitation > II/IV
- Hospitalisation for heart failure or unplanned visit for worsening heart failure in the last month
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 |
|---|---|---|
| DapagliflozinAlso: ForxigaDapagliflozin (Forxiga) is a very potent selective and reversible inhibitor of SGLT2. | Drug | Dapagliflozin |
Primary outcome
To evaluate changes in left ventricular (LV) extracellular mass index (ECMi) measured by MRI, induced by once-daily dapagliflozin 10mg during 6 months in patients with heart failure and reduced ejection fraction
Time frame: 6 months
MRI measurement of changes in left ventricular extracellular mass index (ECMI) after a 6-month once-daily dapagliflozin 10 mg regimen
29 secondary outcomes
To evaluate myocardial morphology
Time frame: 6 months
To evaluate myocardial morphology
Time frame: 6 months
Left ventricular ejection fraction as a biomarker of myocardial function
Time frame: 6 months
Right ventricular ejection fraction as a biomarker of myocardial function
Time frame: 6 months
Left atrial ejection fraction as a biomarker of myocardial function
Time frame: 6 months
Peak global longitudinal strain as a biomarker of myocardial function
Time frame: 6 months
Peak radial strain as a biomarker of myocardial function
Time frame: 6 months
Peak circumferential strain as a biomarker of myocardial function
Time frame: 6 months
Peak circumferential strain as a biomarker of left atrial function
Time frame: 6 months
Peak circumferential strain as a biomarker of left atrial function
Time frame: 6 months
LV myocardial dense fibrosis (late gadolinium enhancement) as a biomarker of fibrosis
Time frame: 6 months
Intracellular mass index (ICMi) as a biomarker of fibrosis
Time frame: 6 months
Extracellular mass index (ECMi) as a biomarker of fibrosis
Time frame: 6 months
To evaluate adipose tissue
Time frame: 6 months
To evaluate myocardial steatosis
Time frame: 6 months
To evaluate glucose metabolism
Time frame: 6 months
Effects of dapagliflozin therapy on the proximal aorta
Time frame: 6 months
Effects of dapagliflozin therapy on the proximal aorta
Time frame: 6 months
Effects of dapagliflozin therapy on the proximal aorta
Time frame: 6 months
Effects of dapagliflozin therapy on the proximal aorta
Time frame: 6 months
Effects of dapagliflozin therapy on the proximal aorta
Time frame: 6 months
To evaluate the evolution of body composition in multimodality imaging
Time frame: 6 months
To evaluate the changes in fasting glucagon
Time frame: 6 months
To evaluate the changes in fasting β-hydroxybutyrate
Time frame: 6 months
To evaluate the changes in fasting glycerol
Time frame: 6 months
To evaluate the changes in free fatty acid (FFA)
Time frame: 6 months
To evaluate the changes in fasting glycemia
Time frame: 6 months
To evaluate the subcutaneous tissue Advanced end-Glycation Products (AGE)
Time frame: 6 months
Evaluation of pathophysiological changes at the molecular level (metabolite profiling)
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2022.
- Individual participant dataSharing planned: Yes. Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission Nationale de l'Informatique et des Libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
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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.
Alban REDHEUIL, MD PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin in people with Heart Failure and Reduced Ejection Fraction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 9 inclusion and 20 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 9 Dec 2022. 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 France. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Alban REDHEUIL, MD PhD (+33(0)1.42.16.55.45, alban.redheuil@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate changes in left ventricular (LV) extracellular mass index (ECMi) measured by MRI, induced by once-daily dapagliflozin 10mg during 6 months in patients with heart failure and reduced ejection fraction (time frame: 6 months). 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 9 Dec 2022.