Safety and Efficacy of Early, seQUential Oral dIuretic Nephron blockAde In Acute Heart Failure

Summary

The SEEQUOIA-AHF (Safety and Efficacy of Early, seQUential oral dIuretic nephron blockAde in Acute Heart Failure) trial is a multicenter, randomized, open-label, parallel-arm trial assessing the impact of early sequential nephron blockade (i.e. a regimen based on the combination of four oral diuretics with different sites of action along the nephron at low doses) compared to a conventional approach with a high-dose loop diuretic in the treatment of congestion in patients hospitalized with acute heart failure (AHF).

In this study, after 24-72 hours of high-dose intravenous furosemide started at the time of hospital admission, patients admitted with AHF will be randomized to open-label oral treatment with either low-dose sequential nephron blockade or high-dose furosemide for 96 hours.

The primary end-point will be the bivariate change in body weight and serum creatinine value at 96 hours since randomization. Secondary endpoints will include clinical (e.g., total change in body weight during hospitalization, change in dyspnea score at 96 hours since randomization, 30-day readmission rate) and laboratory (e.g., change in BNP or NT-proBNP at discharge vs randomization) parameters, and safety (e.g., change in serum creatinine value at discharge versus randomization and up to 30 days from discharge) issues.

Conditions

• Acute Heart Failure

Interventions

DRUG

Standard diuretic therapy

The patients in this arm will be randomized to receiving oral furosemide in 2 daily divided doses at twice the intravenous dose administered during the past 24 hours. Unless serum potassium value is higher than 5 mmol/L, oral spironolactone or potassium canrenoate will be added; dose will be established based on serum creatinine value.

DRUG

Early sequential nephron blockade

After 24-72 hours of an algorithm-based treatment with high-dose intravenous furosemide started at the time of hospital admission, the patients in this arm will be randomized to receiving: 1. oral furosemide in 2 daily divided doses at a dose equivalent to that administered intravenously during the past 24 hours 2. metolazone at a dose based on serum creatinine value 3. acetazolamide at a dose based on serum creatinine value 4. spironolactone or potassium canrenoate (unless serum potassium value is higher than 5 mmol/L); dose will be established based on serum creatinine value

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Parma

  collaborator OTHER

• Azienda USL di Parma

  collaborator UNKNOWN

• Azienda USL Reggio Emilia - IRCCS

  collaborator OTHER_GOV

• University of Parma

  lead OTHER

Principal Investigators

• Enrico Fiaccadori, MD, PhD · Universita degli Studi di Parma

• Giuseppe Regolisti, MD · UO Nefrologia, Azienda Ospedaliero-Universitaria di Parma

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-12-01

Primary Completion

2021-12-01

Completion

2024-12-01

Countries

• Italy

Study Locations