Empagliflozin Versus Placebo on the Rate of Arrhythmic Events in Heart Failure Patients

• Status: Unknown status
• Trial end date: 2020-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Empagliflozin treatment in high cardiovascular risk patients has been shown to have a relatively rapid powerful capability in reducing cardiovascular mortality. Among the suggested mechanisms mediating this effect of empagliflozin, anti-arrhythmic effect (AAE) has the highest potential to translate into a rapid clinical beneficial effect on cardiovascular mortality, while other mechanisms are known to have a lag in their clinical effect based on data from previous studies. Based on this assumption, the study driving hypothesis is that the effect of empagliflozin on the rate of cardiovascular death may be mediated by a direct effect on the risk for arrhythmic events (via a direct or an indirect effect on the myocardium). The current study aims at assessing the effect of empagliflozin on arrhythmias in diabetic patients with HF with reduced ejection fraction and relatively high arrhythmic burden. The objective of the current study is to demonstrate the effect of empagliflozin compared to placebo on the rate of ventricular arrhythmic events in type 2 diabetes patients with heart failure with reduced ejection fraction and high risk arrhythmic profile.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rambam Health Care Campus
• Collaborator: Boehringer Ingelheim
• Treatments: Empagliflozin

Criteria

Inclusion Criteria:

1. Heart failure patients with reduced ejection fraction (EF≤40%) as assessed by echocardiographist least 6 months prior to recruitment and NYHA Class≥2

2. Patients implanted with ICD, CRTD/S or CRTP devices that are capable of recording the PVC burden and implanted ≥ 2 months prior to recruitment.

3. High risk for arrhythmic events at baseline identified by either PVC burden ≥0.5% or ≥2 events of non sustained VT or ≥1 event of sustained ventricular tachycardia or need for anti-tachycardia pacing or defibrillation therapy, during a period of 2 months prior to recruitment.

4. Diagnosis of type 2 diabetes mellitus prior to informed consent

5. HbA1c≥7% and ≤12%.

6. Signed and dated written informed consent by date of Visit 1 in accordance with GCP legislation

-

Exclusion Criteria:

1. Evidence of ICD malfunction.

2. Past exposure to SGLT2 inhibitors.

3. Uncontrolled diabetes with HbA1c>12% or glucose >240 mg/dL after an overnight fast.

4. Liver abnormalities defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal.

5. Planned cardiac procedure within 3 months.

6. Prior MI in the last 40 days.

7. Calculated eGFR< 45ml/min/1.73m2 as determined by the MDRD formula GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)

8. BMI>50

9. Medical History of active cancer in the last 2 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).

10. History of recurrent UTIs or genital infections

11. Systolic blood pressure< 90 mmHg.

12. Alcohol or drug abuse within 3 months of informed consent.

13. Pre-menopausal women (last menstruation <+ 1 year prior to informed consent) who:

• - are nursing or pregnant or

• - are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method and vasectomised partner.

14. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial involving an investigational drug and/or follow-up

-