Effect of Dapagliflozin on myocardial and renal function following aortic valve stenosis intervention

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Midtjylland, Region Midtjylland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

4 Jul 2024 → ongoing

Decision date (initial)

2024-07-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk Foundation

External identifiers

EU CT number

2024-514868-11-00

EudraCT number

2021-004271-14

ClinicalTrials.gov

NCT05241431

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The overall purpose of this study is to improve treatment of aortic stenosis (AS) patients treated with transcatheter aortic valve replacement (TAVR).
The study evaluates the effect of Dapagliflozin on mitochondrial function, myocardial fibrosis, left ventricular hypertrophy, systolic function, renal function, incidence of worsening heart failure and mortality. This will test the potential beneficial effects of Dapagliflozin on myocyte function, interstitial fibrosis, LVH, systolic dysfunction, renal dysfunction, incidence of worsening HF and mortality in AS patients treated with TAVR.

Conditions and MedDRA coding

Aortic stenosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Signed informed consent
2. 2. Scheduled TAVR for significant symptomatic AS according to current guidelines
3. 3. Age < 18 years and < 85 years.
4. 4. LVEF >/= 40% and </= 50 % or LVEF > 50% with at least one of the following: - LV GLS < 15% by TTE - LV septum or posterior wall thickness >/= 12mm by TTE or LV mass index >/= 108/131 g/m2 for females/males (mild LVH) - LVEF > 50 % and Nt-proBNP > 600/900 ng/l (sinus rhythm/atrial fibrillation)
5. 5. eGFR > 30 mL/min/1.73 m2

Exclusion criteria 12

1. 1. Medically treated type 1 or type 2 diabetes mellitus
2. 2. Ongoing treatment with an SGLT2-inhibitor or intolerance to SGLT2-inhibitors
3. 3. Life expectancy < 12 months
4. 4. Symptomatic hypotension or persistent SBP < 100 mmHg
5. 5. Contraindications to CMRI
6. 6. HF due to restrictive or infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis or hypertrophic obstructive cardiomyopathy
7. 7. Additional other untreated severe valvular disease
8. 8. Liver failure
9. 9. Women who are pregnant or plan to be within the study period.**
10. 10. Allergy to any substance in the project medicine, both placebo and active medicine.
11. 11. Previous renal transplantation.
12. 12. Chronic dialysis treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes from baseline to 12 months of follow-up in at least 2 out of 4 well-known parameters of performance in AS is required to reach the primary endpoint. The level of change, in percentage points (%P), is considered clinically significant based on existing litterature: • LVMi reduction of 10 % point (by CMRI) • LV GLS absolute increase of 2.0 % point (by TTE) • A decrease in serum Nt-proBNP of more than 25% • Relative increase of 10% in eGFR

Secondary endpoints 16

1. 1. Difference in the change in eGFR from baseline to 12-months
2. 2. Difference in eGFR at 12-months.
3. 3. The number of patients with a relative difference of 10 % of myocardial interstitial fibrosis evaluated by the biomarker extracellular volume (ECV) by late enhancement gadolinium by CMR
4. 4. The number of patients with a >10% decrease in cardiac fibrosis when assessed by CMR using native T1-mapping.
5. 5. Composite endpoint of worsening HF with hospitalization or urgent outpatient clinical visit due to HF, and all-cause mortality
6. 6. All-cause mortality
7. 7. Worsening HF with hospitalization or urgent outpatient clinical visit due to HF
8. 8. Difference in the change in urinary albumin/creatinine ratio (ACR) from baseline to 12-months.
9. 9. Difference in ACR at 12-months.
10. 10. 24-hour ambulatory blood pressure changes from baseline to 12 months.
11. 11. Change from baseline to 12-months follow-up in the KCCQ Total Symptom Score
12. 12. Change from baseline to 12-months follow-up in NYHA-class
13. 13. LVMi reduction of 10 % point (by CMRI) from baseline to 12-months follow-up
14. 14. LV GLS absolute increase of 2.0 % point (by TTE) from baseline to 12-months follow-up
15. 15. A decrease in serum Nt-proBNP of more than 25% from baseline to 12-months follow-up
16. 16. Relative increase of 10% in eGFR measured at baseline and 12-months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Midtjylland

Sponsor organisation

Region Midtjylland

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus Universitetshospital

Contact name

Anders Lehmann Dahl Pedersen

Public contact point

Organisation

Aarhus Universitetshospital

Contact name

Anders Lehmann Dahl Pedersen

Third parties 1

Region Midtjylland

Sponsor organisation

Region Midtjylland

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications