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

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ClinicalTrials.gov Identifier: NCT02901184
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : June 22, 2021
Sponsor:
Collaborators:
Karolinska University
Duke Clinical Research Institute
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Uppsala University

Tracking Information
First Submitted Date  ICMJE September 9, 2016
First Posted Date  ICMJE September 15, 2016
Last Update Posted Date June 22, 2021
Actual Study Start Date  ICMJE November 23, 2017
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
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) ]
Sweden: Information on Death from the Swedish Causes of death registry and information on hospitalization collected from Swedish Patient Registry US: Collected in eCRF or via call center interview
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
Time to death from any cause [ Time Frame: Collected at data base lock, five (5) years after study start ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
  • 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) ]
    Sweden: Information on Death from the Swedish Causes of death registry US: Collected in eCRF or via call center interview
  • 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) ]
    Sweden: Information on Death from the Swedish Causes of death registry US: Collected in eCRF or via call center interview
  • 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) ]
    Sweden: Information on Death from the Swedish Causes of death registry and information on hospitalization collected from Swedish Patient Registry. US: Collected in eCRF or via call center interview
  • 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) ]
    Sweden: Information on information on hospitalization collected from Swedish Patient Registry. US: Collected in eCRF or via call center interview
  • Time to all-cause mortality [ Time Frame: Collected at data base lock, five (5) years after study start ]
    Sweden: Information on Death from the Swedish Causes of death registry. US: Collected in eCRF or via call center interview
  • 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) ]
    Sweden: Information on information on hospitalization collected from Swedish Patient Registry. US: Collected in eCRF or via call center interview
  • 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) ]
    Sweden: Information on information on hospitalization collected from Swedish Patient Registry. US: Collected in eCRF or via call center interview
  • 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) ]
    Sweden: Information on Death from the Swedish Causes of death registry and information on hospitalization collected from Swedish Patient Registry. US: Collected in eCRF or via call center interview
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
Time to first hospitalization for heart failure [ Time Frame: Collected at data base lock, five (5) years after study start ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction
Official Title  ICMJE Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction, SPIRRIT-HFPEF
Brief Summary

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 (2550 patients) and HFPEF patients in US (650 patients). 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 3 years and study duration 5 years. For the primary outcome (CV Death or first HF hospitalization) with an event target of 632 events the sample size requires 3012 patients conservatively rounded to approximately 3200 patients. A detailed feasibility assessment shows that there will be > 8197 eligible patients to meet the required enrollment of 3200 patients.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure With Preserved Ejection Fraction
Intervention  ICMJE
  • Drug: Spironolactone
    Treatment with Spironolactone tablets on top of standard care
  • Other: Standard care
    Standard care does not involve Spironolactone
Study Arms  ICMJE
  • Active Comparator: 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.
    Intervention: Drug: Spironolactone
  • Placebo Comparator: Standard care alone
    Patients in the control arm will get the standard care alone
    Intervention: Other: Standard care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2019)
3200
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2016)
3500
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anna Gustavsson (SWE) +46186110181 anna.gustavsson@ucr.uu.se
Contact: Jacqueline Huvane (US) 919-668-8282 Jacqueline.Huvane@duke.edu
Listed Location Countries  ICMJE Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02901184
Other Study ID Numbers  ICMJE U-2015-030
U01HL134679-01 ( U.S. NIH Grant/Contract )
U01HL134694-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Current Responsible Party Uppsala University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Uppsala University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Karolinska University
  • Duke Clinical Research Institute
  • National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Lars H Lund, MD, PhD Karolinska Institutet
Principal Investigator: Bertram Pitt University of Michigan
PRS Account Uppsala University
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP