Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction SPIRRIT-HFpEF

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

23 Nov 2017 → ongoing

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Swedish Research Council · The Swedish Heart-Lung Foundation · The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) · The Erling Persson Family Foundation

External identifiers

EU CT number

2024-517448-79-00

EudraCT number

2016-002019-16

ClinicalTrials.gov

NCT02901184

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to assess whether the initiation of spironolactone or eplerenone plus standard of care compared to standard of care alone reduces the incidence rate for total heart failure (HF) hospitalizations or cardiovascular (CV) death in HFpEF, studied with the pragmatic Registry-based Randomized Clinical Trial (RRCT) methodology.

Secondary objectives 1

1. The secondary objectives are to study the secondary endpoints listed below and the primary and secondary endpoints in pre-specified sub-groups.

Conditions and MedDRA coding

Heart failure with preserved ejection fraction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written informed consent
2. Age ≥50 years
3. Stable heart failure defined by symptoms and signs of heart failure as judged by local Investigator. Patients may be enrolled as an outpatient or in-hospital at, or close to, the time of hospital discharge
4. Most recent left ventricular ejection fraction (LVEF) ≥40%
5. Elevated natriuretic peptide levels as defined by any of the following: a. 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. b. 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. c. NT-proBNP >1200 ng/L (or BNP >400 pg/mL) within the last 12 months even if most recent value is lower
6. Regular use of loop diuretics, defined as daily or most days of the week
7. NYHA Class II-IV

Exclusion criteria 15

1. Previously enrolled in this study
2. Known EF <40% ever
3. Current absolute indication or contraindication for MRA in judgement of Investigator. In the absence of absolute indication, patients currently treated with an MRA may have the MRA discontinued and then included in the trial according to investigator judgement
4. Known chronic liver disease
5. Probable alternative explanations for symptoms such as: (a) Known primary cardiomyopathy that is hypertrophic with obstruction, constrictive, restrictive, infiltrative, or congenital (hypertrophic without current obstruction and other primary cardiomyopathies are allowed) (b) Primary valve disease (to exclude a patient, the valve disease must be primary AND the primary cause of the symptoms) (c) Significant chronic pulmonary disease requiring home O2 (d) Symptomatic anemia (hemoglobin is <10 g/dL (100 g/L) and this is the likely cause of the symptoms) (e) Right-sided HF not due to left sided HF
6. Heart transplant or LVAD recipient
7. Presence of cardiac resynchronization therapy (CRT) device
8. Systolic blood pressure <90 or >160 mm Hg at baseline (assessments documented in Medical Records within 30 days) *. *) Blood pressure taken by the patient themselves at home is accepted if no other data is documented within 30 days. The home measurement needs to be noted in Medical Records
9. K >5.0 mmol/L (non-hemolysis sample**; most recent, not older than 30 days). **) All K values in the trial refer to non-hemolysis samples. If hemolysis, blood test needs to be repeated.
10. eGFR by MDRD < 30 ml/min/1.73m2 (most recent, not older than 30 days)
11. Current dialysis
12. Current lithium use
13. Actual or potential for pregnancy
14. Participation in another interventional clinical trial where a mineralocorticoid receptor antagonist is studied. Co-enrollment in trials and observational studies of other medical and device interventions is permitted
15. Not suitable in the opinion of the Investigator due to severe or terminal comorbidity with poor prognosis, or characteristics that may interfere with adherence to trial protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence rate for total heart failure (HF) hospitalizations or cardiovascular (CV) death.

Secondary endpoints 8

1. Time to CV death or first HF hospitalization
2. Time to CV death
3. Incidence rate for total HF hospitalizations
4. Time to HF hospitalization
5. Time to all-cause mortality
6. Incidence rate for total all-cause hospitalizations
7. Time to all-cause hospitalization
8. Incidence rate for all-cause hospitalization or all-cause mortality

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors. Uppsala Domkyrkofors.

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Stefan James

Public contact point

Organisation

Region Uppsala

Contact name

Sara Hansson

Locations

1 EU/EEA country · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications