Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction

Официальное название

Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction, SPIRRIT-HFPEF

Обзор

Heart failure with preserved ejection fraction (HFPEF) is common and deadly but without therapy. Inconclusive studies such as TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) suggest spironolactone may be effective in HFPEF, but it is generic and will not be studied by industry. SPIRRIT is a unique Registry-Randomized Clinical Trial (RRCT) that will test the hypothesis that spironolactone plus standard of care compared to standard of care alone reduces the composite of CV mortality and HF hospitalization as follows: Population: HFPEF patients in the Swedish Heart Failure Registry and HFPEF patients in US. HFPEF defined as symptoms/signs of HF, elevated NTproBNP (B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide) and EF\>=40%. Intervention and control: Randomized 1:1 to intervention: spironolactone + usual care vs. control: usual care alone. Outcome: Primary outcome cardiovascular death or time to HF hospitalization. Secondary outcomes include hospitalization for various causes, adverse events and treatment adherence. In Sweden outcomes are obtained automatically by linking with the Population, Patient and Drug Dispensed Registries. In the US, outcomes will be reported by sites and supplemented by data from a call center. The trial is event-driven with enrollment 7 years and study duration 9 years. For the primary outcome (CV Death or first HF hospitalization) with an event target of 721 events the sample size requires 1985 patients conservatively rounded to approximately 2000 patients.

Вмешательства

• Препарат Spironolactone
  Treatment with Spironolactone tablets on top of standard care
• Другое Standard care
  Standard care does not involve Spironolactone

Первичные конечные точки

• Incidence rate for total heart failure (HF) hospitalizations or cardiovascular (CV) death [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Вторичные конечные точки (8)

• Time to CV Death or first HF hospitalization [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]
• Time to CV Death [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]
• Incidence rate for total HF hospitalizations [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]
• Time to HF hospitalizations [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]
• Time to all-cause mortality [Срок оценки: Collected at data base lock, five (5) years after study start]
• Incidence rate for all-cause hospitalizations [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]
• Time to all-cause hospitalizations [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]
• Incidence rate for all-cause hospitalizations or all-cause mortality [Срок оценки: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Критерии участия

Критерии включения

• Written informed consent
• Age ≥50 years
• Stable heart failure defined by symptoms and signs of heart failure as judged by local Investigator
• Left ventricular ejection fraction (LVEF) ≥40% recorded in last 12 months (stratified to max 2/3rd in either 40-49% or ≥50% group)
• Elevated natriuretic peptide levels, as defined by any of the following:

• most recent NT-proBNP >300 ng/L (or BNP>100 pg/mL) in sinus rhythm at time of blood sampling; adjustments may be made for BMI according to table 3.
• most recent NT-proBNP >750 ng/L (or BNP >250 pg/mL) in atrial fibrillation at time of blood sampling; adjustments may be made for BMI according to table 3.
• NT-proBNP >1200 ng/L (or BNP >400 pg/mL) within the last 12 months even if most recent value is lower.
• Regular use of loop diuretics, defined as daily or most days of the week
• NYHA Class II-IV

Критерии исключения

Previously enrolled in this study

• Known Ejection Fraction < 40% ever
• Current absolute indication or contraindication for MRA (mineral receptor antagonist) in judgement of Investigator
• Known chronic liver disease
• Probable alternative explanations for symptoms:

• Known primary cardiomyopathy (hypertrophic, constrictive, restrictive, infiltrative, congenital)
• Primary hemodynamically significant valve disease
• Right-sided HF not due to left-sided HF
• Significant chronic pulmonary disease defined by Investigator or by requirement for home O2
• Symptomatic anemia, defined as Hemoglobin < 10 g/dL (100 g/L )
• Heart transplant or LVAD (left ventricular assist device) recipient
• Presence of cardiac resynchronization therapy (CRT) device
• Systolic blood pressure <90 or >160 mmHg
• K (potassium) >5.0 mmol/L
• eGFR (estimated glomerular filtration rate) by MDRD (Modification of Diet in Renal Disease) < 30 ml/min/1.73m2 or creatinine > 2.5 mg/dL (221 µmol/L )
• Current lithium use
• Current dialysis
• Actual or potential for pregnancy
• Participation in another interventional clinical trial where a mineralocorticoid receptor antagonist is studied
• Any condition that in the opinion of the Investigator may interfere with adherence to trial protocol

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швеция · 40 центров

• Angereds närsjukhus — Angered
• Hälsostaden Ängelholms sjukhus — Ängelholm
• Falu lasarett — Falun
• Närsjukvården i Finspång — Finspång
• Vårdcentralen Centrum i Flen — Flen
• Sahgrenska University Hospital Östra — Gothenburg
• Sahlgrenska Universitetssjukhuset — Gothenburg
• Hemse Vårdcentral — Hemse
• … и ещё 32 центра

США · 38 центров

• Advanced Cardiovascular LLC — Alexander City
• University of Alabama at Birmingham — Birmingham
• Banner - University Medical Group — Tucson
• MedStar Cardiovascular Research Network — Washington D.C.
• Howard University Hospital — Washington D.C.
• Holy Cross Hospital — Fort Lauderdale
• Piedmont Atlanta Hospital — Atlanta
• Wellstar Health System, Inc. — Marietta
• … и ещё 30 центров

Идентификаторы

NCT: NCT02901184 · U-2015-030 · U01HL134679-01 · U01HL134694-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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