Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction (SPIRRIT)
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| ClinicalTrials.gov Identifier: NCT02901184 |
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Recruitment Status :
Recruiting
First Posted : September 15, 2016
Last Update Posted : June 22, 2021
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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 (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 |
| 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 : | June 2022 |
| Estimated Study Completion Date : | June 2022 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Spironolactone
Treatment with Spironolactone tablets on top of standard care |
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Placebo Comparator: Standard care alone
Patients in the control arm will get the standard care alone
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Other: Standard care
Standard care does not involve Spironolactone |
- 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
- 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
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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 |
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)
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Elevated natriuretic peptide levels, as defined by any of the following:
- 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.
- 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.
- 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
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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
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
| Contact: Anna Gustavsson (SWE) | +46186110181 | anna.gustavsson@ucr.uu.se | |
| Contact: Jacqueline Huvane (US) | 919-668-8282 | Jacqueline.Huvane@duke.edu |
Show 82 study locations
| Principal Investigator: | Lars H Lund, MD, PhD | Karolinska Institutet | |
| Principal Investigator: | Bertram Pitt | University of Michigan |
| Responsible Party: | Uppsala University |
| ClinicalTrials.gov Identifier: | NCT02901184 |
| 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: | June 22, 2021 |
| Last Verified: | June 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |