RECRUITING

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

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2017-11-23
Study Completion:2026-12
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT02901184

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:50 Years to 99 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  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
  4. * Left ventricular ejection fraction (LVEF) ≥40% recorded in last 12 months (stratified to max 2/3rd in either 40-49% or ≥50% group)
  5. * Elevated natriuretic peptide levels, as defined by any of the following:
  6. 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.
  7. 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.
  8. 3. NT-proBNP \>1200 ng/L (or BNP \>400 pg/mL) within the last 12 months even if most recent value is lower.
  9. * Regular use of loop diuretics, defined as daily or most days of the week
  10. * NYHA Class II-IV
  1. * Known Ejection Fraction \< 40% ever
  2. * Current absolute indication or contraindication for MRA (mineral receptor antagonist) in judgement of Investigator
  3. * Known chronic liver disease
  4. * Probable alternative explanations for symptoms:
  5. * Known primary cardiomyopathy (hypertrophic, constrictive, restrictive, infiltrative, congenital)
  6. * Primary hemodynamically significant valve disease
  7. * Right-sided HF not due to left-sided HF
  8. * Significant chronic pulmonary disease defined by Investigator or by requirement for home O2
  9. * Symptomatic anemia, defined as Hemoglobin \< 10 g/dL (100 g/L )
  10. * Heart transplant or LVAD (left ventricular assist device) recipient
  11. * Presence of cardiac resynchronization therapy (CRT) device
  12. * Systolic blood pressure \<90 or \>160 mmHg
  13. * K (potassium) \>5.0 mmol/L
  14. * 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 )
  15. * Current lithium use
  16. * Current dialysis
  17. * Actual or potential for pregnancy
  18. * Participation in another interventional clinical trial where a mineralocorticoid receptor antagonist is studied
  19. * Any condition that in the opinion of the Investigator may interfere with adherence to trial protocol

Contacts and Locations

Study Contact

Anna Gustavsson (SWE)
CONTACT
+46186110181
anna.gustavsson@ucr.uu.se
Will Simmons (US)
CONTACT
919-668-0541
will.simmons@duke.edu

Principal Investigator

Lars H Lund, MD, PhD
PRINCIPAL_INVESTIGATOR
Karolinska Institutet
Bertram Pitt
PRINCIPAL_INVESTIGATOR
University of Michigan

Study Locations (Sites)

Advanced Cardiovascular LLC
Alexander City, Alabama, 35010
United States
University of Alabama at Birmingham
Birmingham, Alabama, 35294
United States
Banner - University Medical Group
Tucson, Arizona, 85724
United States
MedStar Cardiovascular Research Network
Washington, District of Columbia, 20010
United States
Howard University Hospital
Washington, District of Columbia, 20060
United States
Holy Cross Hospital
Fort Lauderdale, Florida, 33308
United States
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
United States
Wellstar Health System, Inc.
Marietta, Georgia, 30060
United States
Queens Medical Center
Honolulu, Hawaii, 96813
United States
Fox Valley Clinical Research Center, LLC
Aurora, Illinois, 60506-1400
United States
University of Illinois at Chicago
Chicago, Illinois, 60612
United States
Alexian Brothers Medical Center
Elk Grove Village, Illinois, 60007
United States
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
United States
St. Vincent Medical Group
Indianapolis, Indiana, 46260
United States
Ochsner Medical Center
New Orleans, Louisiana, 85724
United States
Shady Grove Adventist Hospital
Rockville, Maryland, 20850
United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115
United States
Pentucket Medical Associates
Haverhill, Massachusetts, 01830
United States
Charles River Medical Associates
Natick, Massachusetts, 01760
United States
Newton-Wellesley Hospital
Newton, Massachusetts, 02462
United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
United States
Ascension Genesys Hospital
Grand Blanc, Michigan, 48439
United States
The Heart House Haddon Heights
Haddon Heights, New Jersey, 08035
United States
Rutgers University - Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
United States
University of New Mexico Health Science Center
Albuquerque, New Mexico, 87131
United States
University at Buffalo
Buffalo, New York, 14203
United States
Northwell Health - Manhasset
Manhasset, New York, 11030
United States
Mount Sinai Medical Cente
New York, New York, 10029
United States
Mid Carolina Cardiology Research
Charlotte, North Carolina, 28204
United States
Duke University
Durham, North Carolina, 27710-4000
United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267-0542
United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033
United States
Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
United States
Stern Cardiovascular Center
Germantown, Tennessee, 38138
United States
Baylor University Medical Center
Dallas, Texas, 75246
United States
University of Miami Hospital
Miami, Texas, 33136
United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
United States

Collaborators and Investigators

Sponsor: Uppsala University

  • Lars H Lund, MD, PhD, PRINCIPAL_INVESTIGATOR, Karolinska Institutet
  • Bertram Pitt, PRINCIPAL_INVESTIGATOR, University of Michigan

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-11-23
Study Completion Date2026-12

Study Record Updates

Study Start Date2017-11-23
Study Completion Date2026-12

Terms related to this study

Additional Relevant MeSH Terms

  • Heart Failure With Preserved Ejection Fraction