To Establish Whether Dapagliflozin and Spironolactone in Patients With Severe Aortic Stenosis Undergoing Aortic Valve Replacement, Result in Better Left Ventricular Mass Regression, Myocardial Health and Patient Reported Outcomes

Официальное название

Regression in Left Ventricular Hypertrophy and Fibrosis in Aortic Stenosis - a Randomised Controlled Trial

Обзор

This trial aims to improve the heart health of people with a narrowed aortic valve called aortic stenosis (AS) who then have aortic valve replacement (AVR) by assessing the change in the mass of the left ventricle. Even after an AVR in many patients the heart is still unable to pump as well and can lead to heart failure. This study will assess if medication used in other causes of heart failure can help participants having an AVR recover better. Researchers will compare two drugs, dapagliflozin and spironolactone, that have been shown to help patients with heart failure who do not have AS, to see if taking one or both medicines together will help patients with AS. There will be four treatment arms: dapagliflozin, spironolactone, dapagliflozin and spironolactone together, and standard of care. These will be taken as one tablet of each IMP per day for 12 months. Participants will have approximately four follow up visits, dependent on the treatment arm - those in an arm with spironolactone will have an extra safety follow up visit. These medicines might help patients after AVR by reducing heart muscle thickness and scarring.

Вмешательства

• Препарат Dapagliflozin (DAPA)
  One tablet of Dapagliflozin once a day for the duration of the trial - 12 months (52 weeks).
• Препарат Spironolactone (drug)
  One tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
• Препарат Spironolactone + Dapagliflozin
  One tablet of Dapagliflozin and one tablet of Spironolactone once a day for the duration of the trial - 12 months (52 weeks).
• Препарат Epleronone
  If a participant experiences significant side effects of Spironolactone they will be switched to Epleronone in line with clinical care.

Первичные конечные точки

• Change in the left ventricular mass indexed from pre Aortic Valve Replacement (AVR) to 12 months post AVR [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Participants ≥ 18 years
• Left Ventricular Ejection Fraction (LVEF) ≥40%.
• Diagnosed with severe symptomatic aortic stenosis\* by a cardiologist or cardiac surgeon.

o Severity of AS follows international guideline criteria \[38\], namely at least one out of: effective orifice area \[EOA\] <1.0 cm2, indexed EOA of ≤0.6 cm2/m2, peak velocity ≥4.0 m/s or mean gradient >40 mmHg. \* including severe low flow low gradient AS

• Referred for surgical or transcatheter AVR (SAVR or TAVI).
• Able to provide informed consent and comply with study procedures.

Критерии исключения

• Current use or intolerance or hypersensitivity to MRAs or SGLT2-inhibitors.
• Hyperkalaemia (K>4.5 mmol/L)
• Significant renal impairment (eGFR < 45 mL/min/1.73m²)
• Severe hepatic insufficiency
• Concomitant severe other valve lesion (severe MR, MS or AR)
• Contraindications to MRAs including:

• Addison's disease.
• Acute porphyrias.
• Receiving potassium-sparing diuretics, potassium supplements or strong inhibitors of CYP 3A4 (for example. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone).
• Contraindications to SGLT2-inhibitors including:

• Active urinary tract infections.
• At risk or with a history of diabetic ketoacidosis
• Type 1 or Type 2 Diabetes on insulin.
• Concomitant diagnosis affecting trial participation or life expectancy of less than two years as evaluated by the treating clinician.
• Contraindications to MRI (e.g. non-conditional cardiac pacemaker, severe claustrophobia, inability to lie flat: participants who do not meet local safety rules for MRI). NB: Conditional pacemakers/ICDs, if implanted after the baseline scan, are not an exclusion, depending on local expertise.
• Ongoing participation in another CTIMP interventional clinical trial (i.e. drug trial), will not be permitted. Participation in any other trial will need to be discussed with the trial investigators.
• Significant comorbidities that would contraindicate participation, including uncontrolled hypertension, or recent myocardial infarction (within 3 months prior to screening).
• Pregnancy or breastfeeding, or females of childbearing potential not using an effective method of contraception.
• Any other medical or psychiatric condition that would interfere with participation or compliance with study procedures as determined by the Principal Investigator (PI).

• As evidenced by features of decompensated cirrhosis e.g. hepatic encephalopathy, ascites, jaundice or markedly deranged liver blood tests e.g. elevated bilirubin, serum albumin <30 or deranged clotting

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07539259 · 181443 · NIHR170907

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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