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

Repurposing Empagliflozin for Duchenne Muscular Dystrophy - Associated Cardiomyopathy: a Pharmacokinetics, Safety and Proof-of-concept Study Among Children 6-18 Years of Age

This study aims at exploring the use of empagliflozin in children and adolescents 6-18 years old with Duchenne muscular distrophy (DMD) - associated cardiomyopathy. This molecule is effective in reducing hospitalizations and mortality in adults with heart failure and is used in adolescents with type 2 diabetes mellitus, but little is known on children and adolescents with heart failure. Particularly, the best dose to use in this population is currently unknown. This trial aims to:

1. define a dose rationale for this indication and age group (pharmacokinetic study),
2. assess and monitor safety,
3. assess ease-of-swallow,
4. explore middle-term (3-6 months) efficacy and efficacy markers.

Participants will be asked to attend 5 study visits over 6 months, and one end-study visit 2-12 weeks thereafter. Visit 1 will entail an 8h day-hospital stay, while Visits 2, 3, 4 and 5, as well as the end-study visit, will be outpatient clinics (approximately 2h). Participants will be asked to take the studied drug once daily during the 6 months of the study period.

No comparison group is foreseen for this study.

Study Overview

• Status: Not yet recruiting
• Conditions: DMD-associated Dilated Cardiomyopathy
• Intervention / Treatment: Drug: Empagliflozin Tablets

Detailed Description

Cardiac disease represents the main life-limiting condition in Duchenne muscular dystrophy (DMD). It is important to recognize and address this early in the disease course. Because of lack of DMD specific drugs, present attitudes for established DMD-related cardiomyopathy ground on current treatment for heart failure. Unfortunately, however, current heart failure therapy in Paediatrics is still unsatisfactory, with high in-hospital (7-26%), and 5-year mortality (30%-50%). Furthermore, mortality rate for DMD cardiomyopathy is worse than similarly aged idiopathic dilated cardiomyopathy (DCM) patients.

Among the recent improvements in adult heart failure management, the sodium glucose transporter type 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin were found to reduce cardiovascular death or worsening heart failure by 25% on top of optimal medical therapy. Indeed, since 2021, they have been recommended as part of standard heart failure therapy.

In the past, paediatric heart failure trials often failed, mainly because of suboptimal dose or inappropriate formulations and endpoints.

This phase II.a, open-label trial is designed to characterize pharmacokinetics (primary outcome), ease-of-swallow, safety and explore potential efficacy markers (secondary outcomes) of empagliflozin in 12 children and adolescents with DMD-related cardiomyopathy, so to inform the design and performance of subsequent, state-of-the-art, high-quality efficacy trials.

Participants will receive empagliflozin during 6 months. They will have 5 visits, one end-study visit and 7 to 8 pharmacokinetic samples. The timing of these samples will be optimized exploiting contemporary modeling and simulation techniques.

Safety evaluation will occur throughout the study, while ease-of-swallow will be evaluated at Visit 1, and efficacy markers at Visits 1, 4 and 5.

Pharmacokinetic modeling will characterize primary and secondary pharmacokinetic parameters and allow to define the optimal paediatric dose, informing both current compassionate-care use and the design of future efficacy trials.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Inability to understand and go through the informed consent procedure.
• Inability to receive medications per os or through a nasogastric tube.
• Type 1 or Type 2 Diabetes mellitus or any underlying metabolic disease associated with hypoglycaemias.
• Body weight <15kg.
• Current smokers (defined as >1 cigarette/week).
• Use of any other nicotine-delivering product (e.g. nicotine patches).
• Any known illicit drug abuse.
• Active chronic HBV, HCV or HIV.
• Any major surgery within 4 weeks of first dose administration.
• Blood transfusion recipient within 4 weeks of dose administration.
• eGFR <45mL/min/1.73m2 (simplified Schwartz formula or Filler formula).
• K+ >6.5mmol/L.
• Blood glucose <4mmol/L.
• There are no blood pressure exclusion criteria foreseen, but participants need to be haemodynamically stable, as assessed by the local investigator.
• Sustained or symptomatic arrhythmia insufficiently controlled with drug and/or device therapy.
• 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).
• 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.
• Known lactose intolerance, galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
• Known allergies to active ingredients or excipients of commercially available empagliflozin tablets.
• Significant medical history of active severe medical disease.
• Significant liver disease, Child Pugh Class C, or significant laboratory abnormalities at enrolment.
• Significant gastroenterological or hepatic disease that could significantly impair absorption or metabolism of orally administered drugs.
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin; All participants will receive the IMP (open-label trial, primary outcome PK)	Drug: Empagliflozin Tablets; Empagliflozin 10mg p.o. once daily (commercially available tablet)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - apparent clearance (CL/F)	Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling & simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including CL/F).	Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)
Pharmacokinetics - apparent (central) volume of distribution (Vd/F)	Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling & simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including Vd/F).	Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)
Pharmacokinetics - half-life	Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling & simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including t1/2).	Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)
Pharmacokinetics - AUC	Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling & simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including AUC).	Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)
Pharmacokinetics - maximal concentration (Cmax)	Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling & simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including Cmax).	Time Frame: Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety 1 - eGFR	Creatinine, respectively Cystatin C, will be collected in order to calculate eGFR (bedside Schwartz formula, respectively Filler equation).	Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Safety 2 - Occurrence of hypoglycemia	Blood glucose will be checked three times at Visit 1 (baseline, at approximately 2-3h post-intake, and before discharge at 8h post-intake), as well as once at Visits 2 to 5. Outcome measure: number of patients experiencing hypoglycemia.	Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Safety 3 - Occurrence of ketoacidosis	The outcome is presence (or absence) of ketoacidosis. This will be assessed at Visits 1, 2, 3, 4 and 5. Outcome measure: number of patients experiencing ketoacidosis.	Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Safety 4 - Occurrence of UTI	The outcome is presence (or absence) of UTI diagnosis. This will be assessed at Visits 1, 2, 3, 4 and 5. Outcome measure: number of patients experiencing UTI between Visit 2 and Visit 5.	Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Ease of swallow	Ease of swallow will be assessed by means of facial hedonic scales, according to our standard procedure, at Visit 1. (Scale 1 to 4, 1 being the worse and 4 the best score: very difficult - difficult - possible - easy to swallow.)	Visit 1 (Visit 1 = day 1)
Efficacy and efficacy markers (exploratory) 1 - Heart failure severity class	Symptoms, clinical signs, NYHA (if > or =8 years of age) / Ross (if <8 years of age) class assignment. NYHA and Ross heart failure classes share the same scale of I (no limitation of physical activity) to IV (symptoms at rest). Analysis will be performed at Visit 1, Visit 4 and Visit 5. Outcome: change between Visit 1 and Visit 5.	Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 2 - NT-proBNP level	Analysis will be performed at Visits 1, 3, 4 and 5. Outcome: change between Visit 1 and Visit 5.	Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 3 - Echocardiography 1: Left-ventricular end-diastolic diameter (LVEDd)	LVEDd (z-score) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.	Visits 1, 4 and 5 (Visit 1 = day 1, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 4 - Echocardiography 2: Left-ventricular end-systolic diameter (LVESd)	LVESd (z-score) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.	Visits 1, 4 and 5 (Visit 1 = day 1, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 5 - Echocardiography 3: Fractional shortening (FS)	FS (%) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.	Visits 1, 4 and 5 (Visit 1 = day 1, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 6 - Echocardiography 4: Left ventricular ejection fraction (LV-EF)	LV-EF (%) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.	Visits 1, 4 and 5 (Visit 1 = day 1, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 7 - cMRI 1: Left ventricular end-diastolic volume	LV end-diastolic volume will be measured at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.	Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 8 - cMRI 2: Left ventricular end-systolic volume	LV end-systolic volume will be measured at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.	Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 9 - cMRI 3: Left ventricular ejection fraction	LV end-systolic ejection fraction will be measured/calculated at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.	Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment
Efficacy and efficacy markers (exploratory) 10 - cMRI 4: Presence of late gadolinium enhancement	Presence (y) or absence (n) of late gadolinium enhancement in each of the 17 AHA segments will be measured at Visits 1 and 5. Outcome: change in number of LGE positive segments between Visit 1 and Visit 5.	Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment)
Efficacy and efficacy markers (exploratory) 11 - cMRI 5: Extracellular volume (ECV)	Extracellular volume (ECV) will be measured/calculated at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.	Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy markers (exploratory), Mechanistic insights - 1: body weight (kg)	To explore the effect of SGLT2 inhibitors on fluid status, body weight will be assessed (outcome: change between Visit 1 and Visit 5).	Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)
Efficacy markers (exploratory), Mechanistic insights - 2: heart rate (bpm)	To explore the effect of SGLT2 inhibitors on sympathetic activation, heart rate (in bpm) will be assessed (outcome: change between Visit 1 and Visit 5).	Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)
Efficacy markers (exploratory), Mechanistic insights - 3: blood pressure (SBP/DBP, mmHg)	To explore the effect of SGLT2 inhibitors on sympathetic activation, blood pressure (SBP and DBP, in mmHg) will be assessed (outcome: change between Visit 1 and Visit 5).	Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)
Efficacy markers (exploratory), Mechanistic insights - 4: b-hydroxybutyrate (mmol/L)	To explore the effect of SGLT2 inhibitors on metabolism shift, b-hydroxybutyrate will be assessed (outcome: change between Visit 1 and Visit 5).	Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)
Efficacy markers (exploratory), Mechanistic insights - 5: haemoglobin (g/L)	To explore the effect of SGLT2 inhibitors on haemoglobin, haemoglobin will be assessed (outcome: change between Visit 1 and Visit 5).	Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)
Efficacy markers (exploratory), Mechanistic insights - 6: uric acid (mmol/L)	To explore the effect of SGLT2 inhibitors on uric acid homeostasis, uric acid will be assessed (outcome: change between Visit 1 and Visit 5).	Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)

Collaborators and Investigators

• Sponsor: Sebastiano Lava
• Collaborators: University College, London; Centre Hospitalier Universitaire Vaudois; Great Ormond Street Hospital for Children NHS Foundation Trust

Publications and helpful links

General Publications

• Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28.
• Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, Cox GF, Lurie PR, Hsu D, Canter C, Wilkinson JD, Lipshultz SE. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006 Oct 18;296(15):1867-76. doi: 10.1001/jama.296.15.1867.
• Authors/Task Force Members:; McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022 Jan;24(1):4-131. doi: 10.1002/ejhf.2333.
• Das BB. Current State of Pediatric Heart Failure. Children (Basel). 2018 Jun 28;5(7):88. doi: 10.3390/children5070088.
• Rossano JW, Kim JJ, Decker JA, Price JF, Zafar F, Graves DE, Morales DL, Heinle JS, Bozkurt B, Towbin JA, Denfield SW, Dreyer WJ, Jefferies JL. Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study. J Card Fail. 2012 Jun;18(6):459-70. doi: 10.1016/j.cardfail.2012.03.001. Epub 2012 Apr 10.
• Andrews RE, Fenton MJ, Dominguez T, Burch M; British Congenital Cardiac Association. Heart failure from heart muscle disease in childhood: a 5-10 year follow-up study in the UK and Ireland. ESC Heart Fail. 2016 Jun;3(2):107-114. doi: 10.1002/ehf2.12082. Epub 2016 Jan 24.
• Cella M, Knibbe C, Danhof M, Della Pasqua O. What is the right dose for children? Br J Clin Pharmacol. 2010 Oct;70(4):597-603. doi: 10.1111/j.1365-2125.2009.03591.x. No abstract available.
• Bellanti F, Della Pasqua O. Modelling and simulation as research tools in paediatric drug development. Eur J Clin Pharmacol. 2011 May;67 Suppl 1(Suppl 1):75-86. doi: 10.1007/s00228-010-0974-3. Epub 2011 Jan 19.
• Bellanti F, Di Iorio VL, Danhof M, Della Pasqua O. Sampling Optimization in Pharmacokinetic Bridging Studies: Example of the Use of Deferiprone in Children With beta-Thalassemia. J Clin Pharmacol. 2016 Sep;56(9):1094-103. doi: 10.1002/jcph.708. Epub 2016 Apr 1.
• Lava SA, Simonetti GD, Bianchetti AA, Ferrarini A, Bianchetti MG. Prevention of vitamin D insufficiency in Switzerland: a never-ending story. Int J Pharm. 2013 Nov 30;457(1):353-6. doi: 10.1016/j.ijpharm.2013.08.068. No abstract available.
• Braunwald E. Gliflozins in the Management of Cardiovascular Disease. N Engl J Med. 2022 May 26;386(21):2024-2034. doi: 10.1056/NEJMra2115011. No abstract available.
• Adorisio R, Mencarelli E, Cantarutti N, Calvieri C, Amato L, Cicenia M, Silvetti M, D'Amico A, Grandinetti M, Drago F, Amodeo A. Duchenne Dilated Cardiomyopathy: Cardiac Management from Prevention to Advanced Cardiovascular Therapies. J Clin Med. 2020 Oct 1;9(10):3186. doi: 10.3390/jcm9103186.
• Bourke JP, Bueser T, Quinlivan R. Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy. Cochrane Database Syst Rev. 2018 Oct 16;10(10):CD009068. doi: 10.1002/14651858.CD009068.pub3.
• Muntoni F. Cardiomyopathy in muscular dystrophies. Curr Opin Neurol. 2003 Oct;16(5):577-83. doi: 10.1097/01.wco.0000093100.34793.81.
• Bourke J, Turner C, Bradlow W, Chikermane A, Coats C, Fenton M, Ilina M, Johnson A, Kapetanakis S, Kuhwald L, Morley-Davies A, Quinlivan R, Savvatis K, Schiava M, Yousef Z, Guglieri M. Cardiac care of children with dystrophinopathy and females carrying DMD-gene variations. Open Heart. 2022 Oct;9(2):e001977. doi: 10.1136/openhrt-2022-001977.
• Lava SAG, Laurence C, Di Deo A, Sekarski N, Burch M, Della Pasqua O. Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review. Paediatr Drugs. 2024 May;26(3):229-243. doi: 10.1007/s40272-024-00623-z. Epub 2024 Apr 18.
• Verhaert D, Richards K, Rafael-Fortney JA, Raman SV. Cardiac involvement in patients with muscular dystrophies: magnetic resonance imaging phenotype and genotypic considerations. Circ Cardiovasc Imaging. 2011 Jan;4(1):67-76. doi: 10.1161/CIRCIMAGING.110.960740. No abstract available.
• Loss KL, Shaddy RE, Kantor PF. Recent and Upcoming Drug Therapies for Pediatric Heart Failure. Front Pediatr. 2021 Nov 11;9:681224. doi: 10.3389/fped.2021.681224. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Laminopathies; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Cardiomegaly; Cardiomyopathies; Cardiomyopathy, Dilated; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: 24HL14; 2024-000201-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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