REWORD-HF REverse WOrsening Renal Function in Decompensated Heart Failure

Acute Decompensated Heart Failure Clinical Trial

— REWORD-HF  

Official title:

Impact of Different Therapeutic Approaches in Patients With Cardiorenal Syndrome in the Setting of Acute Decompensated Congestive Heart Failure (ADCHF)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01140399
• Other study ID #: EudraCT code 2009-014
• Secondary ID: FO001
• Status: Terminated
• Phase: Phase 4
• First received: June 7, 2010
• Last updated: April 7, 2017
• Start date: February 2011
• Est. completion date: April 2017

Study information

• Verified date: April 2017
• Source: Niguarda Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: April 2017
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Cardio-Renal Syndrome
• Heart Failure

Intervention

Drug:
• Furosemide or Furosemide and Dopamine
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.

Device:
• Ultrafiltration
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

Locations

Country	Name	City	State
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	Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge	Cassano Murge	Bari
Italy	Azienda Ospedaliera Sant'Anna - Cardiology	Como
Italy	Ospedale SS Annunziata Cardiology	Cosenza
Italy	Azienda Istituti Ospitalieri di Cremona Cardiology	Cremona
Italy	Ospedale Civile di Legnano Cardiology	Legnano	Milano
Italy	Azienda Ospedaliera Niguarda - Heart Failure and Heart Transplant Program	Milano
Italy	Centro Cardiologico Monzino, I.R.C.C.S. Cardiology Intensive Care	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	Ospedale Guglielmo da Saliceto Cardiology Department	Piacenza
Italy	Istituto Clinico Humanitas - IRCCS Clinical Cardiology Cardiovascular Department	Rozzano	Milano
Italy	AO Verona Ospedale Civile Maggiore Cardiology Unit	Verona

Sponsors (2)

Lead Sponsor	Collaborator
Niguarda Hospital	Associazione Nazionale Medici Cardiologi Ospedalieri

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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	Changes in the dyspnea Likert scale		Measured at day 4, at day 10, at day 90 vs baseline
Secondary	Changes in modified RIFLE (AKIN) stage		Measured at day 4 vs baseline
Secondary	Length of stay during index admission		Measured at average day 10
Secondary	Occurrence of major adverse events	All cause mortality, hospital readmission and unscheduled office and emergency department visits for ADCHF	Measured at day 90
Secondary	Days spent alive and out of hospital (DAOH) within 90 days	Sum of days spent alive and out of hospital	Measured at day 90
Secondary	BNP changes	Changes in BNP at specified times VS baseline	Measured at day 0, at day 4, at 10 and day 90
Secondary	Changes in neutrophil gelatinase associated lipocalin (NGAL)	Changes in NGAL at specified times VS screening	Measured at day -1, at day 0 and day 4
Secondary	Changes in Cystatin C (CysC)	Changes in Cystatin C (CysC) at specified times VS baseline	Measured at day 0, day 4, day 10 and day 90
Secondary	Treatment-related adverse events	Bleeding, thrombosis, clotting, infection	Measured at day 4
Secondary	Adverse changes in blood pressure, heart rate and rhythm	Hypotension (< 90 mmHg), tachycardia (> 110 bpm) arrhythmias	Measured at day 4
Secondary	Adverse changes in lab parameters	Hyper-Azotemia (>180 mg/dl), hyper-kaliemia (6.5 mEq/l), hemoconcentration (hematocrit >45%)	Measured at day 4