Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 50 - 99 |
| Updated: | 2/6/2019 |
| Start Date: | November 23, 2017 |
| End Date: | June 2022 |
| Contact: | Anna Gustavsson (SWE) |
| Email: | anna.gustavsson@ucr.uu.se |
| Phone: | +46186110181 |
Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure With Preserved Ejection Fraction, SPIRRIT-HFPEF
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.
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.
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
We found this trial at
3
sites
Click here to add this to my saved trials
Click here to add this to my saved trials