Overview

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

Status:
Not yet recruiting
Trial end date:
2024-12-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 4
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Parma
Collaborators:
Azienda Ospedaliero-Universitaria di Parma
Azienda Unità Sanitaria Locale Reggio Emilia
Azienda USL di Parma
Treatments:
Canrenoic Acid
Diuretics
Furosemide
Spironolactone
Criteria
Inclusion Criteria:

- Male or non-pregnant female patient, 18 years or older

- Patients admitted to Cardiology or Internal Medicine units with a diagnosis of acute
decompensated heart failure and congestion: NT-proBNP > 1,000 pg/ml or BNP >250 pg/ml,
dyspnea and at least two of the following clinical signs: 2+ pitting edema, pulmonary
edema/pleural effusions at chest x-ray or US body weight increase above usual > 5%
over the last 4 weeks

- Clinically stable patients that can be switched to oral diuretic therapy after 24-72
hours of an algorithm-based treatment with high-dose intravenous furosemide started at
the time of hospital admission

- Patients capable to provide written informed consent

Exclusion Criteria:

- Serum creatinine levels > 3.5 mg per deciliter at admission to the hospital or usual
estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73 m2 by the MDRD or CKD-EPI
formula

- Systolic blood pressure < 90 mmHg at time of enrollment and/or hemodynamic instability
severe enough to require intravenous inotropes, intravenous vasodilators, or both

- Severe arrhythmias with hemodynamic instability or DC shock occurred prior to
randomization

- Ascertained acute coronary syndrome (ACS), or ACS occurred within the last 4 weeks

- Hematocrit > 45%

- Use of iodinated radio contrast material occurred in the last 72 hours

- Current mechanical ventilator support

- Previous solid organ transplant

- Primary hypertrophic or infiltrative cardiomyopathy, active myocarditis, constrictive
pericarditis or cardiac tamponade, severe valvular stenosis

- Complex congenital heart disease

- Liver disease (serum ALT or AST > 4, and/or total serum bilirubin > 3)

- Known bilateral renal artery stenosis

- Active sepsis or ongoing systemic infection

- Active gastrointestinal tract bleeding

- Enrollment in another clinical trial

- Locally advanced or metastatic cancer