Stratified Treatment to Ameliorate Diastolic Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction

NCT ID: NCT04475042

Last Updated: 2020-09-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2022-05-31

Brief Summary

A 35-week, single-center, prospective, double-blind, controlled, randomized, 2x2 crossover, interventional Phase II study, investigating the effect of treatment with dapagliflozin 10mg od on Left Ventricular distensibility in patients with early HFpEF.

Conditions

Heart Failure, Diastolic

Study Design

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

Study Groups

Group A

Dapagliflozin - washout period - placebo

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

10mg od

Placebo

Intervention Type: DRUG

Placebo

Group B

Placebo - washout period - Dapagliflozin

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

10mg od

Placebo

Intervention Type: DRUG

Placebo

Interventions

Dapagliflozin

10mg od

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years at time of screening

2. Symptomatic chronic heart failure patients with diagnosis of heart failure and:

• NYHA class II-IV
• Preserved systolic Left Ventricular (LV) function, defined by: LV Ejection Fraction (LVEF) ≥ 50% and LV end-diastolic volume index <97 ml/m2
• Evidence of diastolic LV dysfunction and at least 1 out of the 5 following additional criteria:

1. H2FPEF score ≥ 6;

2. HFA-PEFF score ≥ 5;

3. Pulmonary capillary wedge pressure > 15 mmHg at rest or > 25 mmHg with exercise assessed with right heart catheterization;

3. Cardiac MRI T1 derived extracellular volume <29% at screening

4. Oral diuretics, if prescribed to the patient according to local guidelines and at the discretion of the investigator, should be stable for at least 1 week prior to baseline visit

5. Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial

Exclusion Criteria

1. Reduced systolic LV function (LVEF < 50%), measured at any time point in the history of the patient

2. Obstructive coronary artery disease with evidence of ischemia

3. Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to screening visit

4. More than mild valve stenosis

5. More than moderate aortic and/or mitral valve regurgitation

6. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. hemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (stress cardiomyopathy), hypertrophic (obstructive) cardiomyopathy or known pericardial constriction

7. History of mitral valve repair or replacement

8. Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm at screening

9. Acute decompensation that requires intravenous loop diuretics

10. Systolic blood pressure ≥ 180 mmHg. If SBP > 150 mmHg and < 180 mmHg, the patient should be receiving at least 3 antihypertensive drugs at screening or baseline visit

11. Symptomatic hypotension and/or a SBP < 100 mmHg at screening or baseline visit

12. Impaired renal function, defined as eGFR < 30 ml/min/1.73 m2

13. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal or history of cirrhosis with evidence of portal hypertension

14. Hemoglobin < 9 g/dl at screening

15. Chronic obstructive pulmonary disease, more than GOLD class 2

16. Pulmonary function test with FEV1/FVC < 80%

17. Primary pulmonary arterial hypertension

18. Type 1 Diabetes Mellitus

19. History of ketoacidosis

20. Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix or low risk prostate cancer (biopsy Gleason score of ≤ 6 and clinical stage T1c or T2a)

21. Current use or prior use of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor within 3 months prior to screening visit. Discontinuation of a SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor for the purposes of study enrolment is not permitted

22. Pregnancy or lactation

23. Any (clinical) condition that, in the investigator's opinion, would jeopardize patients safety while participating in this trial, or may prevent the patient from adhering to the trial protocol

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

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Mariëlle Scheffer

OTHER

Sponsor Role: lead

Responsible Party

Mariëlle Scheffer

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

OLVG

Amsterdam, North Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Marielle Scheffer, MD

Role: CONTACT

mailcardio.research@olvg.nl

0031205994889

Facility Contacts

Marielle Scheffer

Role: primary

mailcardio.research@olvg.nl

0031205994889

Other Identifiers

19.185

Identifier Type: -

Identifier Source: org_study_id