Systematic Escalation of diuREtics With Natriuresis in Heart Failure Patients: SERENA Trial

Heart Failure Clinical Trial

— SERENA  

Official title:

Systematic Escalation of diuREtics With Natriuresis in Heart Failure Patients: SERENA Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04907123
• Other study ID #: SERENA trial
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 2021
• Est. completion date: January 2025

Study information

• Verified date: May 2021
• Source: University of Turin, Italy
• Contact: Simone Frea, MD
• Phone: +390116335570
• Email: frea.simone[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The present is a multicenter, prospective, randomized, open-label, blinded end-point trial aiming to investigate the clinical benefit of a stepwise, natriuresis-driven diuretic strategy versus standard diuretic treatment in patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) and low early urinary sodium excretion. The study will focus on patients at increased risk of resistance to diuretic therapy. In particular, patients admitted to the emergency department and cardiac intensive care unit due to an on-chronic or de-novo acute decompensated HF episode with a predominantly "wet" profile and low early spot urinary sodium (UNa+) excretion will be considered. Spot natriuresis is a low-cost, non-demanding laboratory test in use to identify diuretic-resistant patients with an inherent poor prognosis. Whether the early identification of diuretic resistant patients and the consequent more aggressive treatment may lead to a better outcome has not been demonstrated by randomized studies. This trial aims to assess if an intensive stepwise diuretic approach guided by systematic urinary output assessment including natriuresis evaluation versus a standard diuretic strategy based on urinary output alone effectively leads to faster euvolemia achievement and better prognosis in a real-world setting.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 198
• Est. completion date: January 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Admission for acute decompensate chronic heart failure or acute de novo heart failure
• Ejection Fraction <40%
• Severe signs and symptoms of congestion with modified wet score = 12
• Spot urinary sodium excretion = 70 mEq/L at 2 hours from first intravenous loop diuretic administration
• Systolic blood pressure =90 mmHg

Exclusion Criteria:

• Reversible etiology of acute heart failure (including acute coronary syndromes, myocarditis, acute pulmonary embolism, acute rhythm disorders, severe organic valve disease)
• Cardiogenic shock at admission or sign of hypoperfusion needing inotropic agents or mechanical circulatory support.
• eGFR lower than 15 ml/min/1.73m2 or dialysis
• Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Heart Failure

Intervention

Other:
• Intensive sodiuria-guided diuretic treatment
Intensive stepwise diuretic treatment based on combined diuresis and urinary sodium assessment
• Standard diuretic treatment
Stepwise diuretic therapy based on diuresis assessment

Locations

Country	Name	City	State
Italy	A.O.U. Città della Salute e della Scienza di Torino	Torino	To

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to oral switch of diuretic treatments	days	90 days
Other	Time to discharge from hospital	days	90 days
Other	Total Urinary output and urine output/40 mg furosemide	ml/mg furosemide	24 and 48 hours
Other	Variation of body weight and body weight/40 mg furosemide	kg/mg furosemide	24 and 48 hours
Other	Variation of NT-proBNP at 48 hours		48 hours
Other	Variation of wet score at 24 and 72 hours		24 and 72 hours
Other	Dyspnea severity variation at 24 and 48 hours assessed by dyspnea Visual Assessment Scale (VAS).		24 and 48 hours
Other	Fluid balance	In/out fluid balance	24, 48 and 72 hours
Other	Time spent in Intensive Cardiac Intensive Care Unit	days	90 days
Primary	Evidence of significant reduction of congestion defined as absolute reduction of at least 1 point in wet score grading of congestion after 48 hours of treatment	Assessment of WET score (Gheorghiade et al, EJHF 2010)	48 hours
Secondary	Treatment failure, defined as persistent congestion (graded by wet score =12/20) after 24, 48 and 72 hours of diuretic treatment or need for renal replacement therapy.		24,48 and 72 hours
Secondary	Freedom from congestion at 48 hours, defined as jugular venous pressure of <8 cm, with no orthopnea and with trace peripheral edema or no edema		48 hours
Secondary	Worsening or persistent heart failure	worsening heart failure symptoms or failure of the patient's condition to improve with treatment requiring the initiation of intravenous inotropic therapy and/or the implementation of mechanical circulatory or ventilatory support up until 48 hours	48 hours
Secondary	Composite endpoint of all-cause mortality, urgent LVAD implant or Heart Transplantation at 30 and 90 days.		30 and 90 days
Secondary	All-cause mortality		30 and 90 days
Secondary	Cardiac cause mortality	including myocardial infarction, irreversible heart failure, cardiogenic shock, fatal arrhythmic events	30 and 90 days
Secondary	Rehospitalization for heart failure		30 and 90 days
Secondary	Worsening renal function	absolute increase in serum creatinine > 0.3 mg/dl or > 1,5-fold from baseline at any time from randomization to 48 hours	48 hours
Secondary	Incidence of severe hypokalemia, severe hyponatremia or symptomatic electrolytes disorders during treatment protocol	hypokalemia <3 mEq/L, severe hyponatremia <125 mEq/L	72 hours
Secondary	Severe symptomatic hypotension	Systolic arterial pressure < 80 mmHg	72 hours