Clinical trial NCT04907123: Systematic Escalation of diuREtics With Natriuresis in Heart Failure Patients: SERENA Trial
Official title: Systematic Escalation of diuREtics With Natriuresis in Heart Failure Patients: SERENA Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Failure
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2021-05-28
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 48 hours
Secondary outcomes:
measure: 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.
timeFrame: 24,48 and 72 hours
measure: 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
timeFrame: 48 hours
measure: Worsening or persistent heart failure
timeFrame: 48 hours
measure: Composite endpoint of all-cause mortality, urgent LVAD implant or Heart Transplantation at 30 and 90 days.
timeFrame: 30 and 90 days
measure: All-cause mortality
timeFrame: 30 and 90 days
measure: Cardiac cause mortality
timeFrame: 30 and 90 days
measure: Rehospitalization for heart failure
timeFrame: 30 and 90 days
measure: Worsening renal function
timeFrame: 48 hours
measure: Incidence of severe hypokalemia, severe hyponatremia or symptomatic electrolytes disorders during treatment protocol
timeFrame: 72 hours
measure: Severe symptomatic hypotension
timeFrame: 72 hours
Other outcomes:
measure: Time to oral switch of diuretic treatments
timeFrame: 90 days
measure: Time to discharge from hospital
timeFrame: 90 days
measure: Total Urinary output and urine output/40 mg furosemide
timeFrame: 24 and 48 hours
measure: Variation of body weight and body weight/40 mg furosemide
timeFrame: 24 and 48 hours
measure: Variation of NT-proBNP at 48 hours
timeFrame: 48 hours
measure: Variation of wet score at 24 and 72 hours
timeFrame: 24 and 72 hours
measure: Dyspnea severity variation at 24 and 48 hours assessed by dyspnea Visual Assessment Scale (VAS).
timeFrame: 24 and 48 hours
measure: Fluid balance
timeFrame: 24, 48 and 72 hours
measure: Time spent in Intensive Cardiac Intensive Care Unit
timeFrame: 90 days
Locations:
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino
state: To
Study officials:
affiliation: A.O.U. Città della Salute e della Scienza, Torino, Italia
name: Simone Frea, MD
role: PRINCIPAL_INVESTIGATOR
References: