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Trial record 19 of 186 for:    BI10773

Empagliflozin Versus Placebo on the Rate of Arrhythmic Events in Heart Failure Patients (ERA-HF)

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ClinicalTrials.gov Identifier: NCT03271879
Recruitment Status : Not yet recruiting
First Posted : September 5, 2017
Last Update Posted : January 25, 2018
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Rambam Health Care Campus

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.

Condition or disease Intervention/treatment Phase
Heart Failure Diabetes Mellitus Arrythmia Drug: Empagliflozin at a dose of 10 mg/day Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Empagliflozin Versus Placebo on the Rate of Arrhythmic Events in Heart Failure Patients
Estimated Study Start Date : February 15, 2018
Estimated Primary Completion Date : September 1, 2019
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Empagliflozin at a dose of 10 mg/day
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
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
Other Name: JARDIANCE at a dose of 10mg/day

Placebo Comparator: Placebo
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
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
Other Name: JARDIANCE at a dose of 10mg/day




Primary Outcome Measures :
  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 [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. Non-sustained ventricular tachycardia (NSVT) [ Time Frame: 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 ]
    This is defined as the number of sustained ventricular tachycardia, and/or ventricular fibrillation, and/or tachycardia pacing (ATP) and/or delivery of shock therapy. All the four parameters will be captured on ICD or CRTD/P device interrogation. Sustained VT and NSVT will be captured as a backup information (in case of ICD or CRTD/P malfunction) on Holter ECG.

  2. NT-Pro-BNP [ Time Frame: 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). ]
    NT-Pro-BNP Is a plasma level of B-type Natriuretic Peptide used as a blood test for diagnosing and evaluation the presence/severity of heart failure. The change in NT-Pro-BNP will be evaluated as a marker of heart failure severity.

  3. Left ventricular end diastolic diameter [ Time Frame: 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). ]
    End diastolic diameter is defined as the cross-sectional diameter of the left ventricle, including the septum and the posterior thicknesses in diastole.

  4. Left ventricular ejection fraction (EF) [ Time Frame: Time frames include EF measured on visit 3 (on day 112) versus that measured at the end of visit 5 (on day 196). ]
    Ejection fraction is defined as the ratio of the stroke volume to the end-diastolic volume in the left ventricle as performed by echocardiography and expressed by percentage.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03271879


Contacts
Contact: Oren Caspi, MD 97247772180 orencaspi@gmail.com
Contact: Shmuel Rispler, MD 97247772180 s_rispler@rambam.health.gov.il

Sponsors and Collaborators
Rambam Health Care Campus
Boehringer Ingelheim
Investigators
Principal Investigator: Oren Caspi, MD Rambam MC
  Study Documents (Full-Text)

Documents provided by Rambam Health Care Campus:

Responsible Party: Rambam Health Care Campus
ClinicalTrials.gov Identifier: NCT03271879     History of Changes
Other Study ID Numbers: 605-16
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: IPD will be shared following approval of the submitted research proposal by the researcher applying.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Rambam Health Care Campus:
Diabetes
Heart
Arrhythmia

Additional relevant MeSH terms:
Diabetes Mellitus
Heart Failure
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Empagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs