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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 : February 4, 2019
Sponsor:
Collaborators:
Karolinska University
Duke Clinical Research Institute
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Uppsala University

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.


Condition or disease Intervention/treatment Phase
Heart Failure With Preserved Ejection Fraction Drug: Spironolactone Other: Standard care Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction, SPIRRIT-HFPEF
Actual Study Start Date : November 23, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
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.
Drug: Spironolactone
Treatment with Spironolactone tablets on top of standard care

Placebo Comparator: Standard care alone
Patients in the control arm will get the standard care alone
Other: Standard care
Standard care does not involve Spironolactone




Primary Outcome Measures :
  1. Time to Cardiovascular (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 and information on hospitalization collected from Swedish Patient Registry US: Collected in eCRF or via call center interview


Secondary Outcome Measures :
  1. 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

  2. Incidence rate for total HF hospitalizations or 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


  3. 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 information on hospitalization collected from Swedish Patient Registry.

    US: Collected in eCRF or via call center interview


  4. 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


  5. 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

  6. 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


  7. 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


  8. 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




Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  • NT-proBNP (the N-terminal prohormone of brain natriuretic peptide) >300 ng/L in sinus rhythm or >750 ng/L in atrial fibrillation as an outpatient or prior to hospital discharge

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
  • Any condition other than heart failure with a life expectancy < 3 years
  • 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 or oral steroids,
    • Hemoglobin < 10 g/dL (100 g/L )
    • Heart rate > 110bpm
    • Any other condition judged by Investigator to be responsible for symptoms and/or signs
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02901184


Contacts
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Contact: Anna Gustavsson (SWE) +46186110181 anna.gustavsson@ucr.uu.se
Contact: Jacqueline Huvane (US) 919-668-8282 Jacqueline.Huvane@duke.edu

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Sponsors and Collaborators
Uppsala University
Karolinska University
Duke Clinical Research Institute
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Lars H Lund, MD, PhD Karolinska Institutet
Principal Investigator: Bertram Pitt University of Michigan

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Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT02901184     History of Changes
Other Study ID Numbers: U-2015-030
U01HL134679-01 ( U.S. NIH Grant/Contract )
U01HL134694-02 ( U.S. NIH Grant/Contract )
First Posted: September 15, 2016    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents