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

NCT03271879 | Unknown Phase 4

• 1 other identifier: 605-16
• Study Type: interventional
• Target: 128
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Heart Failure; Diabetes Mellitus; Arrythmia

Keywords

Diabetes; Heart; Arrhythmia

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the burden of premature ventricular complexes, defined as the PVCs percentage of all beats in a pre-specified period captured on ICD or CRTD/P device

  PVCs burden is defined as the PVCs percentage of all beats in a pre-specified period captured on ICD or CRTD/P device. The change in PVC burden between time on treatment arm versus time on placebo will be calculated and serve as the primary endpoint.

  Time frames include the time frame between visit 2 (on day 56) and visit 3 (on day 112) and that between visit 4 (on day 140) to visit 5 (on day 196)- each period between visits 2 and 3 and visit 4 and 5 contain a time frame of 56 days

Secondary Outcomes (4)

• Non-sustained ventricular tachycardia (NSVT)

  Time frames include the time frame between visit 2 (on day 56) and visit 3 (on day 112) and that between visit 4 (on day 140) to visit 5 (on day 196)- each period between visits 2 and 3 and visit 4 and 5 contain a time frame of 56 days

• NT-Pro-BNP

  Time frames include NT-Pro-BNP measurement on the end of visit 3 (on day 112) versus NT-Pro-BNP level at the end of visit 5 (on day 196).

• Left ventricular end diastolic diameter

  Time frames include left ventricular diastolic diameter measured on the end of visit 3 (on day 112) versus that measured at the end of visit 5 (on day 196).

• Left ventricular ejection fraction (EF)

  Time frames include EF measured on visit 3 (on day 112) versus that measured at the end of visit 5 (on day 196).

Study Arms (2)

Empagliflozin at a dose of 10 mg/day

ACTIVE COMPARATOR

Patients will be treated with 10mg Empagliflozin once daily for 8 weeks. Patient glucose levels will be monitored based on home monitoring during the treatment period.

Drug: Empagliflozin at a dose of 10 mg/day

Placebo

PLACEBO COMPARATOR

Patients will be treated with Placebo once daily for 8 weeks. Patient glucose levels will be monitored based on home monitoring during the treatment period.

Drug: Empagliflozin at a dose of 10 mg/day

Interventions

Empagliflozin at a dose of 10 mg/day DRUG

Comparing empagliflozin versus placebo on the ventricular arrhythmia burden. This study encompass 4 periods for each study subject: screening period of 8 weeks, first treatment period of 8 weeks, washout period of 4 weeks and a second treatment period of 8 weeks in a cross-over design

Also known as: JARDIANCE at a dose of 10mg/day

Empagliflozin at a dose of 10 mg/day; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart failure patients with reduced ejection fraction (EF≤40%) as assessed by echocardiographist least 6 months prior to recruitment and NYHA Class≥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.
• 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.
• Diagnosis of type 2 diabetes mellitus prior to informed consent
• HbA1c≥7% and ≤12%.
• Signed and dated written informed consent by date of Visit 1 in accordance with GCP legislation

You may not qualify if:

• Evidence of ICD malfunction.
• Past exposure to SGLT2 inhibitors.
• Uncontrolled diabetes with HbA1c\>12% or glucose \>240 mg/dL after an overnight fast.
• Liver abnormalities defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal.
• Planned cardiac procedure within 3 months.
• Prior MI in the last 40 days.
• 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)
• BMI\>50
• 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).
• History of recurrent UTIs or genital infections
• Systolic blood pressure\< 90 mmHg.
• Alcohol or drug abuse within 3 months of informed consent.
• 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.

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Boehringer Ingelheim: collaborator

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Oren Caspi, MD

  Rambam MC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oren Caspi, MD

CONTACT

97247772180; orencaspi@gmail.com

Shmuel Rispler, MD

CONTACT

97247772180; s_rispler@rambam.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will receive study drug: empagliflozin or placebo for an exposure period of up to 16 weeks - at the two treatment periods in a crossover design.

Study Record Dates

• First Submitted: July 30, 2017
• First Posted: September 5, 2017
• Study Start: February 15, 2018
• Primary Completion: September 1, 2019
• Study Completion: June 1, 2020
• Last Updated: January 25, 2018

Record last verified: 2018-01