Clinical trial NCT01140399: REWORD-HF REverse WOrsening Renal Function in Decompensated Heart Failure
Official title: Impact of Different Therapeutic Approaches in Patients With Cardiorenal Syndrome in the Setting of Acute Decompensated Congestive Heart Failure (ADCHF)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Acute Decompensated Heart Failure
Keywords: 1 Acute Decompensated Heart Failure
2 Cardiorenal Syndrome
3 Ultrafiltration
4 Dopamine
Lead sponsor: Niguarda Hospital
Sponsor class: OTHER
Collaborators: name: Associazione Nazionale Medici Cardiologi Ospedalieri
First posted: 2010-06-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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

Eligibility criteria: Inclusion criteria

On admission (screening)

* Informed consent
* Age 18-80 years
* NYHA class III - IV
* Signs of pulmonary (pulmonary rales, and interstitial oedema or pleural effusion on chest Xray) and/or systemic congestion (pitting ankle oedema and enlarged liver or ascites and neck vein distension ≥ 7 cm) and weight gain ≥ 2 kg during the previous week
* Glomerular filtration rate ≥ 30 ml/min
* BNP increased \>400 pg/ml (diagnostic cut-off for ADCHF), as confirmatory diagnostic test)

  24 hours after admission (randomization)
* Persistent signs of pulmonary (pulmonary rales, interstitial oedema or pleural effusion on chest Xray) and/or systemic congestion (ankle oedema, enlarged liver or ascites, neck vein distension ≥ 7 cm)
* Serum creatinine or urine output criteria indicative of modified RIFLE (AKI: risk) class at least 1 (increase x 1.5 in serum creatinine or decrease \> 25% in GFR or urine output \< 0.5 ml/Kg/h for more than 6 hours) 29-30 during diuretic infusion

Exclusion criteria

* Chronic kidney disease stage 4-5 (GFR \< 30 ml/min)
* Acute coronary syndromes
* Systolic blood pressure \<90 mm Hg/need for intravenous inotropes
* Hematocrit \> 45%
* Unattainable venous access
* Contraindications to anticoagulation by heparin
* Systemic infection
* Heart transplant

Primary outcomes:
measure: Changes in a composite clinical-lab score
timeFrame: 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
Secondary outcomes:
measure: Changes in the dyspnea Likert scale
timeFrame: Measured at day 4, at day 10, at day 90 vs baseline
measure: Changes in modified RIFLE (AKIN) stage
timeFrame: Measured at day 4 vs baseline
measure: Length of stay during index admission
timeFrame: Measured at average day 10
measure: Occurrence of major adverse events
timeFrame: Measured at day 90
measure: Days spent alive and out of hospital (DAOH) within 90 days
timeFrame: Measured at day 90
measure: BNP changes
timeFrame: Measured at day 0, at day 4, at 10 and day 90
measure: Changes in neutrophil gelatinase associated lipocalin (NGAL)
timeFrame: Measured at day -1, at day 0 and day 4
measure: Changes in Cystatin C (CysC)
timeFrame: Measured at day 0, day 4, day 10 and day 90
measure: Treatment-related adverse events
timeFrame: Measured at day 4
measure: Adverse changes in blood pressure, heart rate and rhythm
timeFrame: Measured at day 4
measure: Adverse changes in lab parameters
timeFrame: Measured at day 4
Other outcomes:
Locations:
city: Cassano Murge
country: Italy
facility: Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge
state: Bari
city: Legnano
country: Italy
facility: Ospedale Civile di Legnano Cardiology
state: Milano
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas - IRCCS Clinical Cardiology Cardiovascular Department
state: Milano
city: Monza
country: Italy
facility: Azienda Ospedaliera S. Gerardo Heart Failure and Cardiomyopathy Clinic
state: Monza Brianza
city: Monza
country: Italy
facility: Gruppo Policlinico di Monza Clinical Cardiology and Heart Failure Unit - Cardiology Department
state: Monza Brianza
city: Ancona
country: Italy
facility: Ospedali Riuniti di Ancona Cardiology Presidio Lancisi
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo - Cardiovascular Medicine
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Cardiology Unit
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Nefrology,Dialysis and Hypertension Unit
city: Como
country: Italy
facility: Azienda Ospedaliera Sant'Anna - Cardiology
city: Cosenza
country: Italy
facility: Ospedale SS Annunziata Cardiology
city: Cremona
country: Italy
facility: Azienda Istituti Ospitalieri di Cremona Cardiology
city: Milano
country: Italy
facility: Centro Cardiologico Monzino, I.R.C.C.S. Cardiology Intensive Care
city: Milano
country: Italy
facility: Azienda Ospedaliera Niguarda - Heart Failure and Heart Transplant Program
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto Cardiology Department
city: Verona
country: Italy
facility: AO Verona Ospedale Civile Maggiore Cardiology Unit
Study officials:
affiliation: Heart Failure Heart Transplant Program, Cardiovascular Department, Niguarda Hospital, Milan, Italy
name: Fabrizio Oliva, MD
role: STUDY_CHAIR
affiliation: Department of Nephrology, Dialysis and Hypertension, Sant'Orsola Malpighi Hospital, Bologna, Italy
name: Antonio Santoro, MD
role: STUDY_CHAIR
References:
citation: Srivastava M, Harrison N, Caetano AFS, Tan AR, Law M. Ultrafiltration for acute heart failure. Cochrane Database Syst Rev. 2022 Jan 21;1(1):CD013593. doi: 10.1002/14651858.CD013593.pub2.