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

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2024
• Main ID: NCT02901184
• Date of registration: 09/09/2016
• Prospective Registration: Yes
• Primary sponsor: Uppsala University
• Public title: Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction SPIRRIT
• Scientific title: Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction, SPIRRIT-HFPEF
• Date of first enrolment: November 23, 2017
• Target sample size: 2000
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02901184
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Sweden, United States

Contacts

• Name: Anna Gustavsson (SWE)

• Name: Lars H Lund, MD, PhD
• Affiliation: Karolinska Institutet

• Name: Bertram Pitt
• Affiliation: University of Michigan

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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:

1. 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.

2. 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.

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

Exclusion Criteria:

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



Age minimum: 50 Years
Age maximum: 99 Years
Gender: All

Health Condition(s) or Problem(s) studied

Heart Failure With Preserved Ejection Fraction

Intervention(s)

Other: Standard care

Drug: Spironolactone

Primary Outcome(s)

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

Secondary Outcome(s)

Time to all-cause hospitalizations [Time Frame: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Time to CV Death or first HF hospitalization [Time Frame: 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 [Time Frame: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Time to HF hospitalizations [Time Frame: 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 [Time Frame: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Time to all-cause mortality [Time Frame: Collected at data base lock, five (5) years after study start]

Incidence rate for total HF hospitalizations [Time Frame: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Time to CV Death [Time Frame: Collected at data base lock, five (5) years after study start (US: continuously until 5 years after study start)]

Secondary ID(s)

U-2015-030

U01HL134679-01

U01HL134694-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Karolinska University

National Heart, Lung, and Blood Institute (NHLBI)

Duke Clinical Research Institute