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

NCT04907123 | Unknown Phase 3

• 1 other identifier: SERENA trial
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

• 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

• Worsening or persistent heart failure

  48 hours

• Composite endpoint of all-cause mortality, urgent LVAD implant or Heart Transplantation at 30 and 90 days.

  30 and 90 days

• All-cause mortality

  30 and 90 days

Other Outcomes (9)

• Time to oral switch of diuretic treatments

  90 days

• Time to discharge from hospital

  90 days

• Total Urinary output and urine output/40 mg furosemide

  24 and 48 hours

Study Arms (2)

UNa+ Driven Intensive Therapy

EXPERIMENTAL

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.

Other: Intensive sodiuria-guided diuretic treatment

Standard Therapy

ACTIVE COMPARATOR

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.

Other: Standard diuretic treatment

Interventions

Intensive sodiuria-guided diuretic treatment OTHER

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

UNa+ Driven Intensive Therapy

Standard diuretic treatment OTHER

Stepwise diuretic therapy based on diuresis assessment

Standard Therapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

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

Torino, To, 10126, Italy

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Simone Frea, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simone Frea, MD

CONTACT

+390116335570; frea.simone@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Cardiologist

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 28, 2021
• Study Start: October 1, 2021
• Primary Completion: October 1, 2024
• Study Completion: January 1, 2025
• Last Updated: May 28, 2021

Record last verified: 2021-05

Locations

IT (1)