Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fractio

Phase 1

• Conditions: heart failure with left ventricular ejection fraction <50%; MedDRA version: 20.0Level: LLTClassification code 10024102Term: Left cardiac failureSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-005394-66-IT
• Lead Sponsor: AZIENDA OSPEDALIERA UNIVERSITARIA SENESE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-23
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

Patients can be included in the study only if they meet the following criteria:
1. Providing informed consent prior to any specific study procedure
2. Female or male non-diabetic outpatients> 18 years
3. Have heart failure with left ventricular ejection fraction <50%, according to the ESC definition [1], such as patients with signs (pulmonary crepitus, peripheral edema, elevated jugular venous pressure) and / or symptoms (dyspnoea, fatigue, ankle swelling) of heart failure, left ventricular ejection fraction <40% or 40-49%.
4. Already on OMT according to ESC HF guidelines [1] (for HFrEF this mainly includes an angiotensin converting enzyme (ACE) inhibitor or sacubitril / valsartan, a beta blocker and a mineralocorticoid receptor antagonist (MRA)).
5. Subjects without severe chronic kidney disease (eGFR with CKD-EPI formula must be = 30 mL / min)
6. Negative pregnancy test (urine or serum) for female subjects of childbearing age.
7. Female subjects must be 1 year postmenopausal, surgically sterile, or use an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in combination with a spermicide) for the duration of the study (from sign the consent) and for 3 months after the last dose of Drug A / placebo to prevent pregnancy. Also, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; Additional barrier methods should be used in combination with the spermicide.
8. Male subjects must be surgically sterile or use an acceptable method of contraception (defined as barrier methods in combination with spermicides) for the duration of the study (from the time they sign the consent) and for 3 months after the last drug dose A / placebo matching to prevent pregnancy in a partner.
9. Subjects who are blood donors should not donate blood during the study and for 3 months after their last dose of Drug A.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 68

Exclusion Criteria

Patients cannot be included in the study if only one of the following exclusion criteria is present:
1. Involvement in study planning and / or conducting (applies to both investigator staff and study site staff)
2. Previous enrollment or randomization in the present study
3. Participation in another clinical study with an investigational product within the past 6 months
4. Previous treatment with any SGLT2 inhibitor
5. Type II diabetes mellitus
6. Atrial fibrillation at the time of enrollment
7. Chronic kidney damage with creatinine clearance <30 ml / min (calculated from the CKD-EPI formula)
8. <18 years
9. For women only - ongoing pregnancy (confirmed with positive pregnancy test)
10. For women only - breastfeeding
11. Poor quality of echocardiographic images that compromises a correct speckle tracking analysis
12. Failure to sign informed consent
13. Persistent toxicities (> CTCAE grade 2) caused by previous anticancer therapies, excluding alopecia
14. Patients on dialysis
15. Patients with known hypersensitivity to Dapagliflozin or to any of the excipients of the product
16. Any concomitant drug known to be associated with Torsades de pointes or potent inducers of cytochrome P450 3A4 (CYP3A4)
17. History of QT prolongation associated with other drugs that required discontinuation of that drug
18. Congenital long QT syndrome
19. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified