Empagliflozin in the Prevention of Cardiotoxicity in Cancer Patients Undergoing Chemotherapy Based on Anthracyclines

Summary

EMPACT (EMPAgliflozin in prevention of chemotherapy-related CardioToxicity) study is a randomized, multi-center, placebo-controlled, double-blind trial to evaluate efficacy of empagliflozin in prevention of left ventricular (LV) dysfunction in patients receiving high cumulative doses of anthracyclines. Diagnosed with cancer, 220 patients without history of heart failure and LV ejection fraction (EF) ≥ 50%, scheduled for high dose anthracyclines (doxorubicin ≥240 mg/m2 or epirubicin ≥540 mg/m2), will be included in the study. They will be randomized to a 10 mg of empagliflozin once daily or to matching placebo in a 1:1 ratio. The primary objective of the EMPACT study is to assess whether prophylactic SGLT-2 inhibitors may prevent a reduction in LVEF after high doses anthracyclines, as evaluated by serial echocardiography on each visit and cardiovascular magnetic resonance (CMR) performed at randomization and on its completion. The secondary composite endpoint includes: all-cause death, cardiovascular (CV) death, myocardial infarction and ischemic stroke. Additional secondary outcome measures include structural myocardial alterations assessed by CMR, decrease in GLS (global longitudinal strain) in echocardiography and changes in cardiac biomarkers. The study will be carried out in accordance with GCP and monitoring will be outsourced to a subcontractor - CRO. The examination will be insured and will begin as soon as the required approvals are obtained.

Eligibility

The study will include patients with diagnosed cancer, diagnosed and qualified for further systemic treatment at the National Institute of Oncology in Warsaw. Patients must give informed and voluntary consent to participate in the study and meet all the conditions for inclusion in the study

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.
2. Age ≥18 years at the time of signing the informed consent.
3. Known neoplastic disease prior to the initiation of chemotherapy with a high dose of anthracyclines (doxorubicin ≥ 240 mg / m2 b.w. or epirubicin ≥ 540 mg / m2 b.w.)
4. No history of heart failure (left ventricular ejection fraction ≥ 50% as assessed by echocardiography).
5. Women of child-bearing age must have a negative serum or urine pregnancy test.
6. All males and females must consent to the use of effective contraception throughout the study period and after study medication is discontinued.
7. Sexually active women of childbearing potential must use 2 effective methods of contraception (abstinence, IUD, oral contraceptive or double barrier device) from informed consent and for at least 6 months after study drug discontinuation
8. Sexually active men and their sexual partners must use effective methods of contraception from the moment they sign their informed consent to participate in the study and for at least 3 months after discontinuation of the study drug.

Exclusion Criteria:

1. History of heart failure
2. Left ventricle systolic dysfunction assessed by echocardiography (LVEF \<50%)
3. Significant valve disease
4. Previous chemotherapy or radiation to the chest
5. Symptomatic hypotension and / or SBP \<100 mmHg at Visit 1 or Visit 2
6. Liver disease, as determined by ALT, AST, or alkaline phosphatase levels above 3 x upper limit of normal (ULN) at visit 1.
7. Renal impairment, defined as eGFR \<20 mL / min / 1.73 m2 or dialysis requirement, as determined at Visit 1.
8. History of ketoacidosis
9. Gastrointestinal surgery or gastrointestinal disturbance that could impair drug absorption
10. Presence of any disease with a life expectancy \<1 year in the opinion of the investigator.
11. Treatment with any SGLT-2 inhibitor for up to 3 months prior to study enrollment.
12. Pregnancy or breastfeeding
13. Drug or alcohol abuse
14. Suspected non-compliance and irregular use of study drug
15. Inability to perform CMR, e.g. claustrophobia, weight\> 120 kg, etc.

Conditions3

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