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Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? (ATRU-4). (EMPA-TROPISM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03485222
Recruitment Status : Completed
First Posted : April 2, 2018
Results First Posted : March 25, 2021
Last Update Posted : March 25, 2021
Sponsor:
Collaborators:
Boehringer Ingelheim
Eli Lilly and Company
Information provided by (Responsible Party):
Juan Badimon, Icahn School of Medicine at Mount Sinai

Brief Summary:

Purpose:

The overall hypothesis of the study is that the benefits attained in the EMPA-OUTCOME were, at least in part, mediated by a glucose-independent mechanism. Thus, to demonstrate the existence of the postulated non-glucose dependent effects, the researchers will investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in heart failure patients with reduced ejection fraction without diabetes.


Condition or disease Intervention/treatment Phase
Cardiovascular Diseases Drug: Empagliflozin Drug: Placebos Phase 4

Detailed Description:

Heart failure (HF) is a frequent co-morbid condition associated with poor prognosis in diabetes, particularly among older patients. HF accounts for more than 1 Million hospitalizations annually in USA. In addition, HF hospitalizations are associated with significant high risk of post-discharge mortality and recurrent hospitalizations. Almost one-half of patients will be re-hospitalized within 6 months and one-third will die within 12 months of discharge. Median survival after HF diagnosis is about 5 years and is similar for HFpEF and heart failure with reduced ejection fraction (HFrEF) patients. Diabetes as co-morbidity multiplies risk of hospital admissions in HF patients.

Type 2 Diabetes Mellitus (T2DM) is a pathological condition characterized by elevated glucose levels and it is associated with high incidence of cardiovascular (CV) events. Several hypoglycemic agents have successfully managed the elevated glucose levels but with little or no impact on CV events. Management of concomitant HF in T2DM is particularly challenging, as some glucose-lowering agents, such as TZDs, are contraindicated in the treatment of HF patients. Thus, there was a need for an oral agent that improved glycemia as well as provided CV benefits. Empagliflozin is the first glucose-lowering agent showing that not only improves glycemic control but also has cardiovascular benefits. The recent EMPA-OUTCOME trial has shown significant reductions in major adverse cardiac events (MACE), cardiovascular mortality, and hospitalization for Heart Failure (HF) by Empagliflozin given on top of standard-of-care therapy for T2DM patients with Cardiovascular disease (CVD). The dramatic change driving the superiority of the primary composite outcome was a significantly lower CV death rate (38% relative risk reduction). In addition, there were also an impressive 35% and 38% relative risk reductions in hospitalization for heart failure (HF) and death from any cause, respectively.

Empagliflozin is a member of a new class of hypoglycemic agents, the SGLT-2 inhibitors. There are a couple of characteristics that single out the SGLT2 inhibitors from other hypoglycemic drugs. One is their low hypoglycemic risk since they act on the urinary excretion of glucose without interfering with the physiologic response to hypoglycemia. And the other is their "positive" cardiovascular effects such as lowering blood pressure, arterial stiffness, urinary microalbuminuria and triglycerides while increasing HDL-Cholesterol levels. Therefore, the combination of the above-mentioned observations led to some investigators to suggest that these benefits may be, at least in part, independent of its hypoglycemic activity and thus, Empagliflozin could be considered a "cardiac" drug.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: EMPA-TROPISM Trial: Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity?
Actual Study Start Date : May 21, 2018
Actual Primary Completion Date : February 13, 2020
Actual Study Completion Date : February 13, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Empagliflozin
10mg once a day
Drug: Empagliflozin
6 months

Placebo Comparator: Placebos
placebo once a day
Drug: Placebos
placebo equivalent for 6 months




Primary Outcome Measures :
  1. Change in Left Ventricle-end Systolic Volume (ESV) [ Time Frame: Baseline and 6 months ]
    End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction of the left ventricle (LV). Change from baseline to study end at 6 months.

  2. Change in LV-end Diastolic Volume (EDV) [ Time Frame: Baseline and 6 months ]
    End-diastolic volume (EDV) is the volume of blood in the left ventricle at end load or filling in (diastole) or the amount of blood in the ventricles just before systole. Change from baseline to study end at 6 months.


Secondary Outcome Measures :
  1. Change in LV-Ejection Fraction Index [ Time Frame: Baseline and 6 months ]
    The volumetric fraction of blood ejected from the left ventricle of the heart with each heartbeat. Change from baseline to study end at 6 months.

  2. Change in VO2 Consumption [ Time Frame: Baseline and 6 months ]
    Oxygen consumption - the amount of oxygen consumed by the tissues of the body, usually measured as the oxygen uptake in the lung, also called the V02max measure. Change from baseline to study end at 6 months.

  3. Change in 6 Min Walk Test [ Time Frame: Baseline and 6 months ]
    The distance covered over a time of 6 minutes. Change from baseline to study end at 6 months.

  4. Change in Kansas Cardiomyopathy Questionnaire (KCCQ-12) [ Time Frame: Baseline and 6 months ]
    The KCCQ-12 is an instrument most widely used to evaluate QoL in Heart Failure (HF) patients. It is a questionnaire containing 12 questions with full scores ranging from 12 (poor quality of life) to 70 (good quality of life). Higher score indicates better quality of life. Change from baseline to study end at 6 months.



Information from the National Library of Medicine

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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:

  • Patients should meet the following inclusion criteria:
  • Ambulatory patients age 18-85 years
  • Diagnosis of Heart failure (NYHA II to III)
  • LVEF<50% on echocardiography or CMRI in the previous 6 months
  • Have stable symptoms and therapy for HF within the last 3 months.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Any history of diabetes by medical history or by any of the established criteria by the American Diabetes Association. It also includes patients with history of diabetes in remission.
  • ACS or cardiac surgery within the last 3 months.
  • Cancer or any other life-threatening condition.
  • Pancreatitis.
  • Glomerular Filtration Rate < 45 ml/Kg/min.
  • Use of continuous parental inotropic agents.
  • Systolic BP < 90 mm Hg.
  • Psychiatric disease incompatible with being in study.
  • Any contraindication to MRI procedures.
  • Any other medical or physical condition considered to be inappropriate by a study physician.

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): NCT03485222


Locations
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United States, New York
Mount Sinai Heart - Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Boehringer Ingelheim
Eli Lilly and Company
Investigators
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Principal Investigator: Juan J Badimon, PhD Icahn School of Medicine at Mount Sinai
  Study Documents (Full-Text)

Documents provided by Juan Badimon, Icahn School of Medicine at Mount Sinai:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Juan Badimon, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT03485222    
Other Study ID Numbers: GCO 17-2457
First Posted: April 2, 2018    Key Record Dates
Results First Posted: March 25, 2021
Last Update Posted: March 25, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Juan Badimon, Icahn School of Medicine at Mount Sinai:
Cardiovascular diseases
Heart Failure
LV remodeling
SGLT-2 Inhibitors
Empagliflozin
Cardiac MRI
Additional relevant MeSH terms:
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Cardiovascular Diseases
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs