Repurposing Empagliflozin and Dapagliflozin for Paediatric Heart Failure: Translational Approach and Dose Rationale

Summary

This study aims at exploring the use of Dapagliflozin and Empagliflozin in children and adolescents 6-18 years old with heart failure. These molecules are effective in reducing hospitalisations and mortality in adults with heart failure and are used in adolescents with type 2 diabetes mellitus, but little is known on children 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 (4-6 weeks) efficacy and efficacy markers.

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

All participants will take both Dapagliflozin and Empagliflozin: 6 will start with Dapagliflozin first (Visits 1-2) and then switch to Empagliflozin (Visits 3-4), while 6 will start with Empagliflozin first (Visits 1-2) and then switch to Dapagliflozin (Visits 3-4). No comparison group is foreseen for this study.

Conditions

• Heart Failure

Interventions

DRUG

Dapagliflozin tablet

Patients randomized to Group A will start with Dapagliflozin on Visit 1 and take Dapagliflozin once daily up to the day before Visit 3. Patients randomized to Group B will start Dapagliflozin once daily on the day of Visit 3, to be continued up to the day preceding Visit 4. Dose: * participants ≤12 year old: 5mg once daily p.o. (commercially available tablet) * participants \>12 year old: 10mg once daily p.o. (commercially available tablet)

DRUG

Empagliflozin Tablets

Patients randomized to Group A will start with Empagliflozin on Visit 1 and take Empagliflozin once daily up to the day before Visit 3. Patients randomized to Group B will start Empagliflozin once daily on the day of Visit 3, to be continued up to the day preceding Visit 4. Dose: Empagliflozin 10mg once daily p.o. (commercially available tablet)

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust

  collaborator OTHER

• University College, London

  collaborator OTHER

• Centre Hospitalier Universitaire Vaudois

  lead OTHER

Principal Investigators

• Sebastiano A.G. Lava, MD MSc · Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

6 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-31

Primary Completion

2025-08-31

Completion

2025-08-31

Countries

• Switzerland
• United Kingdom

Study Locations