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

NCT ID: NCT04907123

Last Updated: 2021-05-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 198 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-31
• Study Completion Date: 2025-01-31

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

UNa+ Driven Intensive Therapy

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.

Group Type: EXPERIMENTAL

Intensive sodiuria-guided diuretic treatment

Intervention Type: OTHER

Intensive stepwise diuretic treatment based on combined diuresis and urinary sodium assessment

Standard Therapy

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.

Group Type: ACTIVE_COMPARATOR

Standard diuretic treatment

Intervention Type: OTHER

Stepwise diuretic therapy based on diuresis assessment

Interventions

Intensive sodiuria-guided diuretic treatment

Intensive stepwise diuretic treatment based on combined diuresis and urinary sodium assessment

Intervention Type: OTHER

Standard diuretic treatment

Stepwise diuretic therapy based on diuresis assessment

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Turin, Italy

OTHER

Sponsor Role: lead

Responsible Party

Simone Frea

MD, Cardiologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simone Frea, MD

Role: PRINCIPAL_INVESTIGATOR

A.O.U. Città della Salute e della Scienza, Torino, Italia

Locations

A.O.U. Città della Salute e della Scienza di Torino

Torino, To, Italy

Countries

Italy

Central Contacts

Simone Frea, MD

Role: CONTACT

Phone: +390116335570

Email: frea.simone@gmail.com

Facility Contacts

Simone Frea, MD

Role: primary

Other Identifiers

SERENA trial

Identifier Type: -

Identifier Source: org_study_id