The purpose of this study is to determine whether in patients with acute decompensated congestive heart failure and the cardiorenal syndrome, i.e. a state in which therapy directed to improve symptoms is limited by further worsening renal function, fluid removal by ultrafiltration is superior to different pharmacological approaches in acutely relieving congestion and preventing further deterioration in renal function and whether it results in longer admission-free survival 90 days after enrolment
Acute decompensated congestive heart failure (ADCHF), the most common single cause of hospitalization over 65 years, results in 4-8% in-hospital mortality and 30-38% incidence of readmissions within 3 months after discharge. While fluid accumulation remains the main factor causing hospitalization, impaired cardiac output in ADHF causes renal arterial underfilling and increased venous pressure, reducing the glomerular filtration rate and causing acute kidney injury. Aggressive therapy is required to alleviate volume overload during hospital admission and achievement of a dry weight is capital in preventing rehospitalisation. Currently diuretics are considered the standard of care for volume overload in ADHF, yet any patients, especially those with advanced HF become soon resistant to standard doses of loop diuretics, so escalating doses and the association of thiazides are often required to achieve effective diuresis, an approach that will progressively worsen renal function, causing the cardiorenal syndrome. When diuretic resistance develops and symptoms persists, mechanical fluid removal via ultrafiltration should be considered. Ultrafiltration is an alternative method of sodium and water removal, that filters plasma water directly across a semipermeable membrane in response to a transmembrane pressure gradient, resulting in an ultrafiltrate that is isoosmotic compared with plasma water, In view of the limits of traditional therapies for the treatment of congestion and concomitant progressive renal dysfunction in ADHF patients, there is a compelling need for additional studies to individuate the better method for fluid removal in volume-overloaded patients and guide management decisions to reduce associated morbidity. The main objectives of the present project are to evaluate whether in patients with acute decompensated congestive heart failure and the cardiorenal syndrome, i.e. a state in which therapy directed to improve CHF symptoms is limited by further worsening renal function, fluid removal by ultrafiltration is superior to different pharmacological approaches in acutely relieving congestion and preventing further deterioration in renal function and whether it results in longer admission-free survival 90 days after enrolment
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Patients randomized to pharmacological treatment receive * either intravenous diuretics at escalating doses up to 20 mg/h * or intravenous diuretics up to 20 mg/h and dopamine infusion at a constant rate of 3 mcg/Kg/m.
All loop diuretics will be discontinued. Rate of fluid removal will be based on the extent of fluid overload as assessed by increase in body weight vs the patient's known dry weight * less than 3 kg 200 ml/h * more than 3 kg and less than 5 kg 300 mlh * more than 5 kg 500 mlh Criteria for achievement of target UF goals are removal of \> 50% and \<70% of fluid excess based on the estimated increase in body weight Diuretic infusion is allowed provided that a minimum of 3 hours after the end of the UF session have elapsed, at a maximum cumulative dose of 100 mg furosemide, till start of the next UF session The use of inotropic agents is prohibited
Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge
Cassano Murge, Bari, Italy
Ospedale Civile di Legnano Cardiology
Legnano, Milano, Italy
Changes in a composite clinical-lab score
Changes in a score derived by summing up changes in dyspnea, weight loss, glomerular filtration rate (GFR), brain natriuretic peptide (BNP)
Time frame: Baseline and 96 h after randomization,precisely:48 h after end of the last UF session in the intervention arm;24 h after end of 72 h infusional drug treatment in the control arm
Changes in the dyspnea Likert scale
Time frame: Measured at day 4, at day 10, at day 90 vs baseline
Changes in modified RIFLE (AKIN) stage
Time frame: Measured at day 4 vs baseline
Length of stay during index admission
Time frame: Measured at average day 10
Occurrence of major adverse events
All cause mortality, hospital readmission and unscheduled office and emergency department visits for ADCHF
Time frame: Measured at day 90
Days spent alive and out of hospital (DAOH) within 90 days
Sum of days spent alive and out of hospital
Time frame: Measured at day 90
BNP changes
Changes in BNP at specified times VS baseline
Time frame: Measured at day 0, at day 4, at 10 and day 90
Changes in neutrophil gelatinase associated lipocalin (NGAL)
Changes in NGAL at specified times VS screening
Time frame: Measured at day -1, at day 0 and day 4
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Istituto Clinico Humanitas - IRCCS Clinical Cardiology Cardiovascular Department
Rozzano, Milano, Italy
Azienda Ospedaliera S. Gerardo Heart Failure and Cardiomyopathy Clinic
Monza, Monza Brianza, Italy
Gruppo Policlinico di Monza Clinical Cardiology and Heart Failure Unit - Cardiology Department
Monza, Monza Brianza, Italy
Ospedali Riuniti di Ancona Cardiology Presidio Lancisi
Ancona, Italy
Ospedali Riuniti di Bergamo - Cardiovascular Medicine
Bergamo, Italy
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Cardiology Unit
Bologna, Italy
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Nefrology,Dialysis and Hypertension Unit
Bologna, Italy
Azienda Ospedaliera Sant'Anna - Cardiology
Como, Italy
...and 6 more locations
Changes in Cystatin C (CysC)
Changes in Cystatin C (CysC) at specified times VS baseline
Time frame: Measured at day 0, day 4, day 10 and day 90
Treatment-related adverse events
Bleeding, thrombosis, clotting, infection
Time frame: Measured at day 4
Adverse changes in blood pressure, heart rate and rhythm
Hypotension (\< 90 mmHg), tachycardia (\> 110 bpm) arrhythmias
Time frame: Measured at day 4
Adverse changes in lab parameters
Hyper-Azotemia (\>180 mg/dl), hyper-kaliemia (6.5 mEq/l), hemoconcentration (hematocrit \>45%)
Time frame: Measured at day 4