Diabetes Mellitus, Type 2Phase 4CARDIA-STIFFNCT04739215
Effects of SGLT2 Inhibition on the Mechanisms of Cardiac Damage in the Diabetic Patient With HFpEF
A Phase 4 study testing Dapagliflozin 10 MG [Farxiga] in people with Diabetes Mellitus, Type 2 and Heart Failure With Preserved Ejection Fraction, run by Hospital General Universitario Gregorio Marañon at 1 site in Spain.
Trial summary
The main aim of this study is to identify the underlying mechanisms of Sodium-glucose co-transporter-2 (SGLT2) inhibitors which are associated to better outcomes in patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Dapagliflozin 10 MG [Farxiga]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteSpain
- Study dates
- 15 Jan 2021to 30 Dec 2022
- Phase
- Phase 4
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of DM2 based on the established criteria: HbA1c ≥ 6.5% (48 mmol / mol) and fasting plasma glucose ≥ 7.0 mmol / L (≥126 mg / dL) or 2-h after overload ≥ 11.1 mmol / L ( ≥ 200 mg / dL).
- LVEF ≥ 50%.
- Diagnosis of ICFEP according to clinical criteria, with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction according to the echocardiographic criteria.
- Stable clinical situation (> 1 month after hospitalization due to IC decompensation).
- Clinical indication of cardiac catheterization.
- Signature of informed consent.
Who cannot join
- Previous treatment with iSGLT2.
- Significant coronary disease.
- Aortic or mitral valve disease ≥ moderate (grades 3 or 4/4 for valve regurgitations)
- Contraindications for dapagliflozin treatment according to the data sheet (hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption, moderate-severe renal failure -CrCl <60 ml / min or eGFR <60 ml / min / 1 , 73 m2-, severe hepatic insufficiency).
- The inclusion/exclusion criteria for Descriptive Study will be the same as previously described without the diagnosis of DM2.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital General Universitario Gregorio Maranon
Madrid, 280007
Javier Bermejo Thomas, MD, PhD, (34) 91 5868815, javier.bermejo@salud.madrid.org
Javier Bermejo Thomas, MD, PhD
About this study
Official title: Effects of Sodium-Glucose Cotransporter 2 Inhibition on the Mechanisms of Cardiac Damage in the Diabetic Patient With Heart Failure With Preserved Ejection Fraction
The main aim of this study is to identify the underlying mechanisms of Sodium-glucose co-transporter-2 (SGLT2) inhibitors which are associated to better outcomes in patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction.
Read the detailed description
Double design study including a clinical trial and a nested case-control study.
- Experimental study (clinical trial): Phase IV, prospective, randomized, double-blind placebo-controlled with 12 months follow-up. Inclusion criteria are: 1) diagnosis of DM2, 2) HF with preserved EF with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction. 3) Stable clinical situation at inclusion. 4) Clinical indication of cardiac catheterization.
Patients will be randomized 1:1 to received Dapagliflozin 10 mg/day or placebo. The main objective is to compare the impact of the drug on LV diastolic properties at the peak of effort and in levels of plasma deposit and cross-linking biomarkers of type I collagen between the two treatment groups at baseline and after 12 months.
52 patients will be recruited.
- Descriptive study: Nested case-control study, considering patients from the experimental study as cases and 10 additional patients with HF with preserved EF but no type 2 DM as controls. The main aim will be compare the histological, molecular, biochemical and biomechanical features of the HFpEF patients with and without DM2.
- Being tested
- Dapagliflozin 10 MG [Farxiga], Placebo
- Keywords
- Diabetes mellitus, Heart Failure
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10 MG [Farxiga]Drug
Dapagliflozin 10 mg / day oral
PlaceboDrug
One Placebo capsule daily oral
| Study group | Role | What they receive |
|---|---|---|
| Clinical Trial: Experimental Arm | Experimental | Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Dapagliflozin (Forxiga) 10 mg, one capsule per day orally. Receives: Drug: Dapagliflozin 10 MG [Farxiga] |
| Clinical Trial: Placebo Arm | Placebo comparator | Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Placebo in a similar pattern. Receives: Drug: Placebo |
| Descriptive Study | No intervention | Patients with heart failure with preserved ejection fraction but with no type 2 diabetes mellitus (n=10). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Main Objective: Impact of iSGLT2 on LV diastolic properties in terms of the change in LV stiffness constant (S+) at the peak of exercise.
Intrinsic diastolic properties will be analyzed by dynamic pressure-volume loop catheterization.
Measured: Baseline vs 12 months
Main Structural Objective: Changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL)
We will measure the changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL), a validated biomarker of collagen type I deposition
Measured: Baseline vs 12 months
Secondary outcomes (8)
Changes in LV stiffness constants (S+ and S-).
LV stiffness constants will be obtained from invasive pressure-volume data analysis.
Measured: Baseline vs 12 months
Changes in the slope, Emax, of the end-systolic pressure-volume relationship
Emax will be obtained from invasive pressure-volume data analysis.
Measured: Baseline vs 12 months
Impact of iSGLT2 on myocardial remodeling.
Reverse cardiac remodeling will be studied by cardiac magnetic resonance (CMR). CMR studies will be performed on 1.5 T scanners and will include short-axis cine steady-state free-precession images from base to apex, and standard long axis views for the analysis of mass, volume and ventricular function.
CMR study will require the administration of a gadolinium contrast medium to study myocardial fibrosis, unless contraindicated.
Measured: Baseline vs 12 months
Correlation of myocardial remodeling patterns with the intrinsic diastolic properties of chamber VI with systolic function.
Results from the pressure-volume analysis and CMR will be assess in common in order to search for association.
Measured: Baseline vs 12 months
Relative contribution of the intrinsic diastolic properties of the LV and the flow patterns on filling pressures and their modulation under treatment with iSGLT2.
Intraventricular flow patterns will be studied by Doppler echocardiography and phase contrast CMR, considering vorticity and blood transport parameters.
Measured: Baseline vs 12 months
Changes in serum levels of collagen type I C-terminal telopeptide to matrix metalloproteinase ratio (CITP:MMP-1)
We will measure the changes in serum levels of collagen type I C-terminal telopeptide to matrix metalloproteinase ratio (CITP:MMP-1), biomarker of the degree of collagen type cross-linking.
Measured: Baseline vs 12 months
Changes in N-terminal pro brain natriuretic peptide (pg/mL)
We will measure the changes in N-terminal pro brain natriuretic peptide (pg/mL)
Measured: Baseline vs 12 months
Changes in high sensitivity troponin T (pg/mL)
We will measure the changes in high sensitivity troponin T (pg/mL)
Measured: Baseline vs 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start15 Jan 2021
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital General Universitario Gregorio Marañon
- Sponsor type
- University, hospital or other
- Collaborators
- University of Navarra, Instituto de Salud Carlos III, Fundación para la Investigación Biomédica del Hospital Gregorio Maranon
- Responsible party
- Sponsor
- Investigators
- Javier Bermejo Thomas, MD, PhD, Principal investigator, Hospital General Universitario Gregorio Marañon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04739215
- Sponsor's protocol ID
- FIBHGM-CARDIA-STIFF
- Other IDs
- 2019-002046-20, 2019
- Acronym
- CARDIA-STIFF
- Status last verified
- Feb 2021
- First submitted
- 15 Jan 2021
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kasner M, Westermann D, Lopez B, Gaub R, Escher F, Kuhl U, Schultheiss HP, Tschope C. Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction. J Am Coll Cardiol. 2011 Feb 22;57(8):977-85. doi: 10.1016/j.jacc.2010.10.024.
PubMed 21329845Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.
PubMed 26378978Perez Del Villar C, Savvatis K, Lopez B, Kasner M, Martinez-Legazpi P, Yotti R, Gonzalez A, Diez J, Fernandez-Aviles F, Tschope C, Bermejo J. Impact of acute hypertension transients on diastolic function in patients with heart failure with preserved ejection fraction. Cardiovasc Res. 2017 Jul 1;113(8):906-914. doi: 10.1093/cvr/cvx047.
PubMed 28402411Bermejo J, Yotti R, Perez del Villar C, del Alamo JC, Rodriguez-Perez D, Martinez-Legazpi P, Benito Y, Antoranz JC, Desco MM, Gonzalez-Mansilla A, Barrio A, Elizaga J, Fernandez-Aviles F. Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function. J Appl Physiol (1985). 2013 Aug 15;115(4):556-68. doi: 10.1152/japplphysiol.00363.2013. Epub 2013 Jun 6.
PubMed 23743396
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sodium-Glucose Cotransporter 2 Inhibition on the Mechanisms of Cardiac Damage in the Diabetic Patient With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT04739215
- Acronym / sponsor ID
- CARDIA-STIFF / FIBHGM-CARDIA-STIFF
- Keywords
- Diabetes mellitus, Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Hospital General Universitario Gregorio MarañonUniversity, hospital or other
- Collaborators
- University of Navarra, Instituto de Salud Carlos III, Fundación para la Investigación Biomédica del Hospital Gregorio Maranon
- Study start
- 15 Jan 2021 (actual)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 4 Feb 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.
The main aim of this study is to identify the underlying mechanisms of Sodium-glucose co-transporter-2 (SGLT2) inhibitors which are associated to better outcomes in patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction.
Detailed description
Double design study including a clinical trial and a nested case-control study.
- Experimental study (clinical trial): Phase IV, prospective, randomized, double-blind placebo-controlled with 12 months follow-up. Inclusion criteria are: 1) diagnosis of DM2, 2) HF with preserved EF with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction. 3) Stable clinical situation at inclusion. 4) Clinical indication of cardiac catheterization.
Patients will be randomized 1:1 to received Dapagliflozin 10 mg/day or placebo. The main objective is to compare the impact of the drug on LV diastolic properties at the peak of effort and in levels of plasma deposit and cross-linking biomarkers of type I collagen between the two treatment groups at baseline and after 12 months.
52 patients will be recruited.
- Descriptive study: Nested case-control study, considering patients from the experimental study as cases and 10 additional patients with HF with preserved EF but no type 2 DM as controls. The main aim will be compare the histological, molecular, biochemical and biomechanical features of the HFpEF patients with and without DM2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Clinical Trial: Experimental Arm | Experimental | Drug: Dapagliflozin 10 MG [Farxiga]Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Dapagliflozin (Forxiga) 10 mg, one capsule per day orally. |
| Clinical Trial: Placebo Arm | Placebo comparator | Drug: PlaceboPatients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Placebo in a similar pattern. |
| Descriptive Study | No intervention | –Patients with heart failure with preserved ejection fraction but with no type 2 diabetes mellitus (n=10). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of DM2 based on the established criteria: HbA1c ≥ 6.5% (48 mmol / mol) and fasting plasma glucose ≥ 7.0 mmol / L (≥126 mg / dL) or 2-h after overload ≥ 11.1 mmol / L ( ≥ 200 mg / dL).
- LVEF ≥ 50%.
- Diagnosis of ICFEP according to clinical criteria, with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction according to the echocardiographic criteria.
- Stable clinical situation (> 1 month after hospitalization due to IC decompensation).
- Clinical indication of cardiac catheterization.
Key exclusion criteria (5 listed)
- Previous treatment with iSGLT2.
- Significant coronary disease.
- Aortic or mitral valve disease ≥ moderate (grades 3 or 4/4 for valve regurgitations)
- Contraindications for dapagliflozin treatment according to the data sheet (hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption, moderate-severe renal failure -CrCl <60 ml / min or eGFR <60 ml / min / 1 , 73 m2-, severe hepatic insufficiency).
- The inclusion/exclusion criteria for Descriptive Study will be the same as previously described without the diagnosis of DM2.
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 |
|---|---|---|
| Dapagliflozin 10 MG [Farxiga]Dapagliflozin 10 mg / day oral | Drug | Clinical Trial: Experimental Arm |
| PlaceboOne Placebo capsule daily oral | Drug | Clinical Trial: Placebo Arm |
Primary outcome
Functional Main Objective: Impact of iSGLT2 on LV diastolic properties in terms of the change in LV stiffness constant (S+) at the peak of exercise.
Time frame: Baseline vs 12 months
Intrinsic diastolic properties will be analyzed by dynamic pressure-volume loop catheterization.
Main Structural Objective: Changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL)
Time frame: Baseline vs 12 months
We will measure the changes in serum levels of procollagen type I C-terminal propertied (PICP, ng/mL), a validated biomarker of collagen type I deposition
8 secondary outcomes
Changes in LV stiffness constants (S+ and S-).
Time frame: Baseline vs 12 months
Changes in the slope, Emax, of the end-systolic pressure-volume relationship
Time frame: Baseline vs 12 months
Impact of iSGLT2 on myocardial remodeling.
Time frame: Baseline vs 12 months
Correlation of myocardial remodeling patterns with the intrinsic diastolic properties of chamber VI with systolic function.
Time frame: Baseline vs 12 months
Relative contribution of the intrinsic diastolic properties of the LV and the flow patterns on filling pressures and their modulation under treatment with iSGLT2.
Time frame: Baseline vs 12 months
Changes in serum levels of collagen type I C-terminal telopeptide to matrix metalloproteinase ratio (CITP:MMP-1)
Time frame: Baseline vs 12 months
Changes in N-terminal pro brain natriuretic peptide (pg/mL)
Time frame: Baseline vs 12 months
Changes in high sensitivity troponin T (pg/mL)
Time frame: Baseline vs 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Results publication: PubMed 21329845Kasner M, Westermann D, Lopez B, Gaub R, Escher F, Kuhl U, Schultheiss HP, Tschope C. Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction. J Am Coll Cardiol. 2011 Feb 22;57(8):977-85. doi: 10.1016/j.jacc.2010.10.024.
- Results publication: PubMed 26378978Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.
- Results publication: PubMed 28402411Perez Del Villar C, Savvatis K, Lopez B, Kasner M, Martinez-Legazpi P, Yotti R, Gonzalez A, Diez J, Fernandez-Aviles F, Tschope C, Bermejo J. Impact of acute hypertension transients on diastolic function in patients with heart failure with preserved ejection fraction. Cardiovasc Res. 2017 Jul 1;113(8):906-914. doi: 10.1093/cvr/cvx047.
- Results publication: PubMed 23743396Bermejo J, Yotti R, Perez del Villar C, del Alamo JC, Rodriguez-Perez D, Martinez-Legazpi P, Benito Y, Antoranz JC, Desco MM, Gonzalez-Mansilla A, Barrio A, Elizaga J, Fernandez-Aviles F. Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function. J Appl Physiol (1985). 2013 Aug 15;115(4):556-68. doi: 10.1152/japplphysiol.00363.2013. Epub 2013 Jun 6.
- Individual participant dataSharing planned: Undecided
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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.
Javier Bermejo Thomas, MD, PhD principal investigator
Hospital General Universitario Gregorio Marañon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin 10 MG [Farxiga] in people with Diabetes Mellitus, Type 2 and Heart Failure With Preserved Ejection Fraction, run by Hospital General Universitario Gregorio Marañon at 1 site in Spain.
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 6 inclusion and 5 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 4 Feb 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 Spain. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Javier Bermejo Thomas, MD, PhD ((34) 91 5868279, javier.bermejo@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Main Objective: Impact of iSGLT2 on LV diastolic properties in terms of the change in LV stiffness constant (S+) at the peak of exercise. (time frame: Baseline vs 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04739215, which also lists 4 linked publications.
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 4 Feb 2021.