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

University of Turin

Status and phase: Not yet enrolling; Phase 3

Conditions: Heart Failure

Treatments: Other: Standard diuretic treatment; Other: Intensive sodiuria-guided diuretic treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT04907123

SERENA trial

Details and patient eligibility

About

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.

Enrollment: 198 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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198 participants in 2 patient groups

UNa+ Driven Intensive Therapy

Experimental group

Description:

Ask patient to empty bladder. Start treatment (step 1). Re-evaluate patient every 6 hours; if therapeutic goal is not met, treat according to the following step. Therapeutic goal: Spot Urinary Sodium \> 70 mEq/L AND mean diuresis \> 1,5 ml/kg/h Step 1 Furosemide i.v. continuous infusion (2 times oral daily dose; minimum dose: 240 mg die) Step 2 Double furosemide i.v. continuous infusion (maximal dose: 720 mg die) Step 3 Add oral metolazone 5 mg b.i.d. Step 4 Add oral acetazolamide 250 mg b.i.d.

Treatment:

Other: Intensive sodiuria-guided diuretic treatment

Standard Therapy

Active Comparator group

Description:

Ask patient to empty bladder. Start treatment (step 1). Re-evaluate patient every 12 hours; if therapeutic goal is not met, treat according to the following step. Therapeutic goal: mean diuresis \> 1,5 ml/kg/h Step 1 Furosemide i.v. continuous infusion (2 times oral daily dose; minimum dose: 240 mg die) Step 2 Double furosemide i.v. continuous infusion (maximal dose: 720 mg die) Step 3 Add oral metolazone 5 mg b.i.d. Step 4 Add oral acetazolamide 250 mg b.i.d.

Treatment:

Other: Standard diuretic treatment