Repurposing Empagliflozin for DMD-associated Cardiomyopathy in Children 6-18 Years of Age

Prior treatment

• Inability to receive medications per os or through a nasogastric tube.
• Any known illicit drug abuse.
• Any major surgery within 4 weeks of first dose administration.
• Cardio-surgical procedure within the 2 months prior to Visit 1, or interventional cardiac catheterization within 2 weeks prior to Visit 1, or the patient is planned to undergo cardiac surgery or an interventional cardiac catheterization during the study period (i.e. in the 6 months following Visit 1).
• Active urinary tract infection (being treated with antibiotics at the moment of Visit 1) or other relevant bacterial infection, as judged by the treating clinician and/or the study investigator.
• The patient is currently participating in another interventional clinical trial or has participated in such a trial during the \<14 days before Visit 1 (or if enrolment in this study is incompatible with the protocol of that preceding trial), or the duration of five half-lives of the IMP, whichever is longer.

Other illness

• Type 1 or Type 2 Diabetes mellitus or any underlying metabolic disease associated with hypoglycaemias.
• Active chronic HBV, HCV or HIV.
• Sustained or symptomatic arrhythmia insufficiently controlled with drug and/or device therapy.
• Known allergies to active ingredients or excipients of commercially available empagliflozin tablets.
• Significant medical history of active severe medical disease.
• Significant gastroenterological or hepatic disease that could significantly impair absorption or metabolism of orally administered drugs.

Lab values

• eGFR \<45mL/min/1.73m2 (simplified Schwartz formula or Filler formula).
• Blood glucose \<4mmol/L.
• Known lactose intolerance, galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
• Significant liver disease, Child Pugh Class C, or significant laboratory abnormalities at enrolment.

Other

• Inability to understand and go through the informed consent procedure.
• Body weight \<15kg.
• Current smokers (defined as \>1 cigarette/week).
• Use of any other nicotine-delivering product (e.g. nicotine patches).
• Blood transfusion recipient within 4 weeks of dose administration.
• K+ \>6.5mmol/L.
• There are no blood pressure exclusion criteria foreseen, but participants need to be haemodynamically stable, as assessed by the local investigator.
• Post-menarchal female patients of childbearing potential cannot be included. Participants who begin menstruating during the trial will be discontinued from the IMP. However, their monitoring will continue up to 6 months after their first dose of IMP.
• Any medical co-morbidity, which is deemed incompatible (or only with relevant risk) with study participation by the treating clinician and/or the study investigator.

• Children or adolescents 6 to 18 years of age with DMD-associated cardiomyopathy, followed either as in- or outpatients, will be eligible for inclusion.
• Currently on heart failure medication (any drug or any combination).
• Patients should potentially benefit from adding a SGLT2i (as judged by the treating physician and the PI or Co-PI).
• Patients need to be on stable medical treatment, defined as no new heart failure drug started over the preceding 2 weeks and no major drug dose modification (apart minor adaptations, like weight adaptations, rounding or formulation changes) during the 2 weeks prior to enrolment.
• Adolescents, respectively parents or caregivers of children, capable of giving informed consent.
• Ability to tolerate a cardiac MRI investigation without the need of general anaesthesia.