Dapagliflozin After Transcatheter Aortic Valve Implantation (DapaTAVI)

Pragmatic, controlled, prospective, randomized, open-label (open-label), evaluator-blind clinical trial (PROBE design) that will analyze the benefits of dapagliflozin treatment in patients with severe aortic stenosis discharged after implantation of an aortic valve prosthesis transcatheter (TAVI).

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Stenosis; Transcatether Aortic Valve Implantation
• Intervention / Treatment: Drug: Dapagliflozin 10 MG

Detailed Description

Patients discharged after TAVI, with a history of heart failure (HF) plus depressed left ventricular ejection fraction (LVEF ≤ 40%) or diabetes mellitus (DM) or glomerular filtration rate (GFR) between 25 and 75 ml/min/1.73 m2, will be randomized (1:1) before hospital discharge to receive treatment with dapagliflozin 10 mg/day or no dapagliflozin (no placebo).

Only variables available during routine clinical practice will be collected and there will be no additional tests.

The incidence of clinical events and adherence to the dapagliflozin arm will be documented at 2 time-points (3 ± 1 months and 12 months) by phone calls and review of medical records.

• Study Type: Interventional
• Enrollment (Estimated): 1020
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: SERGIO RAPOSEIRAS ROUBIN, PhD, MD; Phone Number: 034 620170387; Email: raposeiras26@hotmail.com
• Study Contact Backup: Name: IGNACIO AMAT SANTOS, PhD, MD; Phone Number: 034 657923040; Email: ijamat@gmail.com

Study Locations

• Spain
  • Albacete, Spain
    • Hospital Universitario de Albacete
  • Alicante, Spain
    • Hospital General Universitario de Alicante
  • Barakaldo, Spain
    • Hospital Universitario de Cruces
  • Barcelona, Spain
    • Hospital Universitario Vall d´Hebron
  • Barcelona, Spain
    • Hospital de Bellvitge
  • Barcelona, Spain
    • Hospital Clínic
  • Barcelona, Spain
    • Centro Medico Teknon
  • Barcelona, Spain
    • Hospital Universitario Sant Pau
  • Barcelona, Spain
    • Hospital German I Trias
  • Cadiz, Spain
    • Hospital Puerta del Mar
  • Cordoba, Spain
    • Hospital Reina Sofia
  • Coruña, Spain
    • Hospital Juan Canalejo
  • Granada, Spain
    • Hospital San Cecilio
  • Granada, Spain
    • Hospital Virgen de las Nieves
  • Huelva, Spain
    • Hospital Juan Ramón Jimenez
  • Jaen, Spain
    • Hospital Universitario de Jaén
  • León, Spain
    • Hospital Universitario de León
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital La Princesa
  • Madrid, Spain
    • Hospital Puerta de Hierro
  • Madrid, Spain
    • Clinica La Luz
  • Madrid, Spain
    • Clinica Nuestra Señora de América de Madrid
  • Madrid, Spain
    • Hospital Universitario de Torrejon
  • Málaga, Spain
    • Hospital Virgen de la Victoria
  • Oviedo, Spain
    • Hospital Universitario Central de Asturias
  • Palma De Mallorca, Spain
    • Hospital Son Espases
  • Pamplona, Spain
    • Hospital Universitario de Navarra
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
  • Santander, Spain
    • Hospital Marques de Valdecilla
  • Santiago De Compostela, Spain
    • Hospital Clínico de Santiago
  • Sevilla, Spain
    • Hospital Virgen del Rocío
  • Tenerife, Spain
    • Hospital Universitario de Canarias
  • Valencia, Spain
    • Hospital Clinico de Valencia
  • Valencia, Spain
    • Hospital La Fe
  • Valladolid, Spain
    • Hospital Clínico Universitario de Valladolid
  • Vigo, Spain
    • Hospital Álvaro Cunqueiro
  • Zaragoza, Spain
    • Hospital Miguel Servet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• SEVERE AORTIC STENOSIS UNDERWENT TAVI

• PRIOR HEART FAILURE ADMISSION AND ONE OF THE FOLLOWING CRITERIA:

  1. Left ventricular ejection fraction ≤ 40% or
  2. Diabetes mellitus or
  3. Estimated glomerular filtrate rate 25-75 ml/min/1.73 m2

Exclusion Criteria:

• Known allergy or intolerance to SGLT2 inhibitors.
• Concomitant therapy with sulfonylurea or SGLT2 inhibitors..
• Systolic blood pressure < 100 mmHg or diastolic blood pressure < 50 mmHg.
• An estimated glomerular filtration rate (GFR) below 25 ml per minute per 1.73 m2.
• Chronic cystitis and/or recurrent urinary tract infections (2 or more in the last year)
• Poor control of diabetes mellitus that requires SGLT-2 inhibitor prescription on discharge according to treating physician judge.
• Any medical condition that, in the investigator´s judgment, would seriously limit life expectancy (less than one year).
• Pregnant or breast-feeding patients
• Patients participating in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dapagliflozin; Sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy with daily oral dose of dapagliflozin 10 mg	Drug: Dapagliflozin 10 MG; Dapagliflozin 10 mg (daily oral dose)
No Intervention: Standard care; No SGLT-2 inhibitor therapy with dapagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of the composite of all-cause mortality or worsening heart failure (HF)	All-cause mortality and worsening HF (including hospitalization for HF or an urgent visit resulting in intravenous therapy for HF).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate all-cause mortality	All cause mortality	1 year
Incidence rate of Cardiovascular death	Mortality secondary to cardiovascular cause	1 year
Incidence rate of Hospitalization for Heart Failure	Heart Failure requiring hospital admission	1 year
Incidence rate of Urgent Heart Failure visits	Urgent Heart Failure visit requiring intravenous therapy	1 year
Incidence rate of the composite of Heart Failure hospitalization or Cardiovascular death	Composite of Heart Failure hospitalization or Cardiovascular death	1 year
Total number of Heart Failure hospitalizations and Cardiovascular deaths	Total number of (first and recurrent) Heart Failure hospitalizations and Cardiovascular deaths	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in NYHA class.	Functional class according to New York Heart Association classification	1 year
Rate of treatment switch (crossovers)	Percentage of patients in the "dapagliflozin arm" who stop this treatment and percentage of patients in "standard care" arm who start dapagliflozin therapy	1 year
Incidence of new Atrial Fibrillation	Diagnosis of new Atrial Fibrillation in patients without history of atrial fibrillation at baseline	1 year
Safety endpoints	Symptomatic hypotension. Symptomatic hypotension includes postural dizziness with systolic blood pressure < 100 mmHg, and orthostatic hypotension (defined as a decrease of >20 mmHg in systolic blood pressure or >10 mmHg in diastolic blood pressure from a supine to a standing position).; Major hypoglycemia. Major hypoglucemia is defined as an event where all the following criteria were confirmed by the investigator: (1) the patient experienced symptoms of severe impairment in consciousness or behaviour; (2) the patient needed external assistance; (3) intervention was needed to treat the hypoglycaemia; and (4) there was prompt recovery of acute symptoms following the intervention.; Ketoacidosis.; Genital or Urinary Infections; Amputation; Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)	1 year

Collaborators and Investigators

• Sponsor: Spanish Society of Cardiology
• Collaborators: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Investigators: Study Chair: EMAD ABU ASSI, PhD, MD, University Hospital Alvaro Cunqueiro, Vigo, Spain; Study Director: BORJA IBAÑEZ, PhD, MD, Centro Nacional de Investigaciones Cardiovasculares (CNIC, Madrid, Spain); Principal Investigator: SERGIO RAPOSEIRAS ROUBIN, PhD, MD, University Hospital Alvaro Cunqueiro, Vigo, Spain; Principal Investigator: IGANCIO AMAT SANTOS, PhD, MD, Hospital Clínico Universitario de Valladolid

Publications and helpful links

General Publications

• Amat-Santos IJ, Sanchez-Luna JP, Abu-Assi E, Melendo-Viu M, Cruz-Gonzalez I, Nombela-Franco L, Munoz-Garci AJ, Blas SG, de la Torre Hernandez JM, Romaguera R, Sanchez-Recalde A, Diez-Gil JL, Lopez-Otero D, Gheorge L, Ibanez B, Iniguez-Romo A, Raposeiras-Roubin S; Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) Investigators. Rationale and design of the Dapagliflozin after Transcatheter Aortic Valve Implantation (DapaTAVI) randomized trial. Eur J Heart Fail. 2022 Mar;24(3):581-588. doi: 10.1002/ejhf.2370. Epub 2021 Nov 9.

Helpful Links

• Web Page of DapaTAVI trial

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 30, 2020
• First Submitted That Met QC Criteria: January 3, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Dapagliflozin; Aortic Stenosis; TAVI
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: SEC-DAPATAVI-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data will be available to other researchers after ending the trial, prior to a formal request to the Executive Committee
• IPD Sharing Time Frame: 5 years
• IPD Sharing Access Criteria: Email (dapatavi@gmail.com)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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