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

NCT ID: NCT02901184

Last Updated: 2024-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

2000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-23

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Heart Failure With Preserved Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Spironolactone treatment

Spironolactone will be prescribed by the Investigator and filled by patient at conventional pharmacies as 25 mg tablets. The treatment will be on top of standard care. Initial dose is 25 mg/day, which will be increased to target dose 50 mg/day if tolerated. Eplerenone can be prescribed if spironolactone is not tolerated.

Group Type ACTIVE_COMPARATOR

Spironolactone

Intervention Type DRUG

Treatment with Spironolactone tablets on top of standard care

Standard care alone

Patients in the control arm will get the standard care alone

Group Type PLACEBO_COMPARATOR

Standard care

Intervention Type OTHER

Standard care does not involve Spironolactone

Interventions

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Spironolactone

Treatment with Spironolactone tablets on top of standard care

Intervention Type DRUG

Standard care

Standard care does not involve Spironolactone

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

50 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karolinska University

OTHER

Sponsor Role collaborator

Duke Clinical Research Institute

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Uppsala University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lars H Lund, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Bertram Pitt

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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Advanced Cardiovascular LLC

Alexander City, Alabama, United States

Site Status TERMINATED

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status TERMINATED

Banner - University Medical Group

Tucson, Arizona, United States

Site Status TERMINATED

MedStar Cardiovascular Research Network

Washington D.C., District of Columbia, United States

Site Status TERMINATED

Howard University Hospital

Washington D.C., District of Columbia, United States

Site Status TERMINATED

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status TERMINATED

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status TERMINATED

Wellstar Health System, Inc.

Marietta, Georgia, United States

Site Status TERMINATED

Queens Medical Center

Honolulu, Hawaii, United States

Site Status TERMINATED

Fox Valley Clinical Research Center, LLC

Aurora, Illinois, United States

Site Status TERMINATED

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status TERMINATED

Alexian Brothers Medical Center

Elk Grove Village, Illinois, United States

Site Status TERMINATED

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status TERMINATED

St. Vincent Medical Group

Indianapolis, Indiana, United States

Site Status TERMINATED

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status TERMINATED

Shady Grove Adventist Hospital

Rockville, Maryland, United States

Site Status TERMINATED

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status TERMINATED

Pentucket Medical Associates

Haverhill, Massachusetts, United States

Site Status TERMINATED

Charles River Medical Associates

Natick, Massachusetts, United States

Site Status TERMINATED

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Site Status TERMINATED

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status TERMINATED

Ascension Genesys Hospital

Grand Blanc, Michigan, United States

Site Status TERMINATED

The Heart House Haddon Heights

Haddon Heights, New Jersey, United States

Site Status TERMINATED

Rutgers University - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status TERMINATED

University of New Mexico Health Science Center

Albuquerque, New Mexico, United States

Site Status TERMINATED

University at Buffalo

Buffalo, New York, United States

Site Status TERMINATED

Northwell Health - Manhasset

Manhasset, New York, United States

Site Status TERMINATED

Mount Sinai Medical Cente

New York, New York, United States

Site Status TERMINATED

Mid Carolina Cardiology Research

Charlotte, North Carolina, United States

Site Status TERMINATED

Duke University

Durham, North Carolina, United States

Site Status TERMINATED

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status TERMINATED

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status TERMINATED

Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status TERMINATED

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status TERMINATED

Stern Cardiovascular Center

Germantown, Tennessee, United States

Site Status TERMINATED

Baylor University Medical Center

Dallas, Texas, United States

Site Status TERMINATED

University of Miami Hospital

Miami, Texas, United States

Site Status TERMINATED

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status TERMINATED

Angereds närsjukhus

Angered, , Sweden

Site Status TERMINATED

Hälsostaden Ängelholms sjukhus

Ängelholm, , Sweden

Site Status TERMINATED

Falu lasarett

Falun, , Sweden

Site Status RECRUITING

Närsjukvården i Finspång

Finspång, , Sweden

Site Status TERMINATED

Vårdcentralen Centrum i Flen

Flen, , Sweden

Site Status RECRUITING

Sahgrenska University Hospital Östra

Gothenburg, , Sweden

Site Status RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Site Status RECRUITING

Hemse Vårdcentral

Hemse, , Sweden

Site Status RECRUITING

Karolinska University Hospital

Huddinge, , Sweden

Site Status RECRUITING

Länssjukhuset Ryhov

Jönköping, , Sweden

Site Status RECRUITING

Blekingesjukhuset

Karlskrona, , Sweden

Site Status ACTIVE_NOT_RECRUITING

Hjärtmottagningen, Centralsjukhuset

Karlstad, , Sweden

Site Status RECRUITING

Västmanlands sjukhus Köping

Köping, , Sweden

Site Status RECRUITING

Centralsjukhuset Kristianstad

Kristianstad, , Sweden

Site Status TERMINATED

Lasarettet i Landskrona

Landskrona, , Sweden

Site Status RECRUITING

Skaraborgs sjukhus i Lidköping

Lidköping, , Sweden

Site Status RECRUITING

Linköpings Universitetssjukhus

Linköping, , Sweden

Site Status RECRUITING

VO Akut- och internmedicin, Skånes Universitetssjukhus

Lund, , Sweden

Site Status TERMINATED

Capio Citykliniken

Lund, , Sweden

Site Status RECRUITING

FO Kranskärl/Svikt, Skånes Universitetssjukhus

Lund, , Sweden

Site Status RECRUITING

Hjärtavdelningen, Skånes Universitetssjukhus

Malmo, , Sweden

Site Status TERMINATED

Kliniska forskningsenheten Skånes Universitetssjukhus

Malmo, , Sweden

Site Status RECRUITING

Mariefreds Vårdcentral

Mariefred, , Sweden

Site Status RECRUITING

Sahlgrenska University Hospital Mölndal

Mölndal, , Sweden

Site Status RECRUITING

Kardiologikliniken, Vrinnevisjukhuset

Norrköping, , Sweden

Site Status RECRUITING

Oskarshamns sjukhus

Oskarshamn, , Sweden

Site Status ACTIVE_NOT_RECRUITING

Örebro University Hospital

Örebro, , Sweden

Site Status RECRUITING

Skellefteå lasarett

Skellefteå, , Sweden

Site Status RECRUITING

Karolinska University Hospital

Solna, , Sweden

Site Status RECRUITING

Södertälje sjukhus

Södertälje, , Sweden

Site Status TERMINATED

VO Kardiologi, Södersjukhuset AB

Stockholm, , Sweden

Site Status RECRUITING

Capio S:t Görans sjukhus AB

Stockholm, , Sweden

Site Status RECRUITING

Danderyds sjukhus AB

Stockholm, , Sweden

Site Status RECRUITING

Länssjukhuset Sundsvall-Härnösand

Sundsvall, , Sweden

Site Status RECRUITING

Sundsvalls Vårdcentral

Sundsvall, , Sweden

Site Status TERMINATED

Uppsala University Hospital, Cardiology dept

Uppsala, , Sweden

Site Status RECRUITING

Uppsala University Hospital, Internal Medicine dept

Uppsala, , Sweden

Site Status RECRUITING

Medicinkliniken, Hallands sjukhus

Varberg, , Sweden

Site Status RECRUITING

Västmanlands sjukhus Västerås

Västerås, , Sweden

Site Status RECRUITING

Västerviks sjukhus

Västervik, , Sweden

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Sweden

Central Contacts

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Anna Gustavsson (SWE)

Role: CONTACT

+46186110181

Will Simmons (US)

Role: CONTACT

919-668-0541

Facility Contacts

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Fahed Sulaiman

Role: primary

Kaj Possler

Role: primary

Mikael Fu

Role: primary

Charlotta Ljungman

Role: primary

Ann Hovland-Tånneryd

Role: primary

Lars H Lund

Role: primary

Patric Karlström

Role: primary

Edit Floderer

Role: primary

Emöke Fodor

Role: primary

Fredrik Kymle

Role: primary

Magnus Peterson

Role: primary

Henriette van der Wal

Role: primary

Carl-Johan Lindholm

Role: primary

Grunde Gjesdal

Role: primary

Tobias Reitberger

Role: primary

Pär Parén

Role: primary

Dimitros Ftakas

Role: primary

Barna Szabó

Role: primary

Lars Gustafsson

Role: primary

Lars H Lund

Role: primary

Carin Corovic Cabrera

Role: primary

Majid Jourak

Role: primary

Jonas Spaak

Role: primary

Mohammad Kavianipour

Role: primary

Tymon Pol, MD, Phd

Role: primary

Michael Dimberg

Role: primary

Petru Tutuainu

Role: primary

Ingmar Lönnberg

Role: primary

Other Identifiers

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U01HL134679-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL134694-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U-2015-030

Identifier Type: -

Identifier Source: org_study_id

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