Effects of SGLT2 Inhibition on the Mechanisms of Cardiac Damage in the Diabetic Patient With HFpEF

NCT ID: NCT04739215

Last Updated: 2021-02-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-15
• Study Completion Date: 2022-12-30

Brief 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.

Detailed Description

Double design study including a clinical trial and a nested case-control study.

A) 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.

B) 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.

Conditions

Diabetes Mellitus, Type 2; Heart Failure With Preserved Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Clinical Trial: Experimental Arm

Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Dapagliflozin (Forxiga) 10 mg, one capsule per day orally.

Group Type: EXPERIMENTAL

Dapagliflozin 10 MG [Farxiga]

Intervention Type: DRUG

Dapagliflozin 10 mg / day oral

Clinical Trial: Placebo Arm

Patients with heart failure with preserved ejection fraction and type 2 diabetes mellitus treated with Placebo in a similar pattern.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One Placebo capsule daily oral

Descriptive Study

Patients with heart failure with preserved ejection fraction but with no type 2 diabetes mellitus (n=10).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dapagliflozin 10 MG [Farxiga]

Dapagliflozin 10 mg / day oral

Intervention Type: DRUG

Placebo

One Placebo capsule daily oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Navarra

OTHER

Sponsor Role: collaborator

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

Fundación para la Investigación Biomédica del Hospital Gregorio Maranon

OTHER

Sponsor Role: collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Bermejo Thomas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario Gregorio Marañón

Locations

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Javier Bermejo Thomas, MD, PhD

Role: CONTACT

javier.bermejo@salud.madrid.org

(34) 91 5868279

Facility Contacts

Javier Bermejo Thomas, MD, PhD

Role: primary

javier.bermejo@salud.madrid.org

(34) 91 5868815

References

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.

Reference Type: RESULT

PMID: 21329845 (View on PubMed)

Zinman 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.

Reference Type: RESULT

PMID: 26378978 (View on PubMed)

Perez 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.

Reference Type: RESULT

PMID: 28402411 (View on PubMed)

Bermejo 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.

Reference Type: RESULT

PMID: 23743396 (View on PubMed)

Other Identifiers

2019-002046-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FIBHGM-CARDIA-STIFF

Identifier Type: -

Identifier Source: org_study_id