Clinical trial NCT04618601: Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
Official title: Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure Acute
Heart Failure; With Decompensation
Keywords: diuretic resistance
spironolactone
cardio-renal syndrome
diuretics
natriuresis
heart failure
Lead sponsor: Laikο General Hospital, Athens
Sponsor class: OTHER
First posted: 2020-11-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, single-center, open-label and randomized trial for evaluation of the effect of a 5-day administration of high doses of spironolactone (≥100mg daily) on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with acute decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of care (SOC) in management of heart failure (HF) patients. However, recommended doses of MRAs (up to 50mg daily) have any impact on signs and symptoms of volume overload. Therefore, the proposed study will aim to show the impact of high doses of spironolactone to improve diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.

Detailed description: Congestion represents a hallmark feature of ADHF, which is present in more than 90% of patients hospitalized for this diagnosis. Intravenous loop diuretics are the mainstay of treatment. Nonetheless, nearly half of the patients who are hospitalized for AdHF continue to have residual symptoms and sign of congestion at time of discharge. Various pharmacological and non-pharmacological interventions have been proposed over the past years as potential means for relieving congestion in hospitalized ADHF patients. However, their efficacy has not been shown.

Given that hyperaldosteronism is a key feature in HF, the hypothesis that administration of high doses of spironolactone can potentiate the natriuretic effects of loop diuretics and relieve congestion in the setting of ADHF has been raised.

According to the most recent guidelines spironolactone can be considered in combination with loop diuretic in patients with resistant edema or insufficient symptomatic response. However, spironolactone at a dose of 100 mg daily has failed to increase diuresis in patients with ADHF.

The present study will assess the effect of high per os doses of spironolactone (≥100mg) on top of SOC treatment compared with SOC treatment alone on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of acute heart failure within the past 8 hours
* Two of the following: 1. edema, 2. ascites, 3. jugular vein distention, 4. pulmonary congestion
* NT-proBNP \>1,000 pg/ml or \>3,000 pg/ml (in the presence of atrial fibrillation)
* Per os mean daily loop diuretic dose equivalent to 80 mg of furosemide for at least 1 month prior to presentation and at least one of the following: 1. serum urea/serum creatinine \> 50 at presentation, 2. serum creatinine increased \>0.3 mg/dl compared with previous value (within the last year), 3. serum creatinine \> 1.8 mg/dl.

Exclusion Criteria:

* pregnancy or breast feeding
* current acute coronary syndrome
* significant valvular disease
* pulmonary embolism
* allergy or intolerance to spironolactone
* current mechanical circulatory support
* primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy
* mean arterial pressure \<65mmHg or systolic arterial pressure \<90 mmHg at presentation
* anticipated use of inotropes or vasodilators (other than renal doses of dopamine, i.e. \<2.5 μg/kg/min)
* anticipated need of ultrafiltration
* exposure to nephrotoxic agents within 3 days of presentation
* serum potassium\> 5 mmol/L
* per os receipt of spironolactone or eplerenone in a dose \> 50 mg daily prior to presentation.

Primary outcomes:
measure: Daily urine output
timeFrame: 5 days
Secondary outcomes:
measure: Total urine output
timeFrame: 5 days
measure: Total weight change
timeFrame: 5 days
measure: Daily weight change
timeFrame: 5 days
measure: Natriuresis on days 1, 3 and 5
timeFrame: 5 days
measure: Changes in natriuresis between days 1, 3 and 5
timeFrame: 5 days
measure: Changes in NT-proBNP between days 1 and 5
timeFrame: 5 days
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Laiko General Hospital
state: Attiki
Study officials:
affiliation: Laikon General Hospital
name: John Barbetseas, MD
role: STUDY_CHAIR
References:
citation: Kapelios CJ, Bonou M, Vogiatzi P, Tzanis G, Mantzouratou P, Lund LH, Barbetseas J. Association Between High-Dose Spironolactone and Decongestion in Patients with Acute Heart Failure: An Observational Retrospective Study. Am J Cardiovasc Drugs. 2018 Oct;18(5):415-422. doi: 10.1007/s40256-018-0290-3.