Effect of Dapagliflozin on Myocardial and Renal Function Following Aortic Valve Stenosis Intervention

NCT05241431 | Unknown Phase 2 DMC

• 1 other identifier: DAPAS
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, double-blinded, placebo-controlled study in AS patients with subclinical or clinical heart failure undergoing treatment with TAVR.

Conditions

Aortic Stenosis; Left Ventricle Hypertrophied

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of changes in LV mass, systolic function, eGFR, and serum Nt-proBNP

  Changes from baseline to 12 months of follow-up in at least 2 out of 4 well-known parameters is required to reach the primary endpoint: * LVMi (grams) reduction of 10 % point (by CMRI) * LV GLS (percent) absolute increase of 2.0 % point (by TTE) * A decrease in serum Nt-proBNP (ng/L) of more than 25% * Relative increase of 10% in eGFR (ml/min/1.73m\^2) If 2 or more of the 4 outcome measures are reached at 12-months follow-up, the patient has fulfilled the primary end-point.

  Baseline assesment to 12-months follow-up post-TAVR

Secondary Outcomes (17)

• Difference in the change in eGFR

  baseline to 12-months

• Difference in eGFR

  12-months

• 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

  Baseline to 12-months

• The number of patients with a >10% decrease in cardiac fibrosis when assessed by histology and quantified by stereology (sub study)

  Baseline to 12-months

• The number of patients with an increase in the respiratory control ratio (RCR) by ≥10% measured by High Resolution Respirometry (HRR) (sub study)

  Baseline to 12-months

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

10 mg (oral) SGLT-2 inhibitor once daily

Drug: SGLT2 inhibitor

Control group

PLACEBO COMPARATOR

Placebo tablet encapsulated as the active treatment.

Drug: Placebo

Interventions

SGLT2 inhibitor DRUG

10 mg orally once daily in addition to standard medical treatment.

Intervention group

Placebo DRUG

Placebo tablets similar to active treatment.

Control group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Scheduled TAVR for significant symptomatic AS according to current guidelines
• Age ≥ 18 years and \< 85 years.
• 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)
• eGFR \> 30 mL/min/1.73 m2

You may not qualify if:

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

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis; Hypertrophy, Left Ventricular

Interventions

Sodium-Glucose Transporter 2 Inhibitors

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Cardiomegaly; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Steen Hvitfeldt Poulsen

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anders Lehmann Dahl Pedersen, MD

CONTACT

0045 2785 2009; anlepe@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The medicine will be blinded by encapsulation of both active medicine and placebo in gelatine capsules, in order to blind treatment to both investigators and patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 15, 2022
• Study Start: February 12, 2022
• Primary Completion: March 1, 2024
• Study Completion: April 1, 2024
• Last Updated: February 15, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)