REWORD-HF REverse WOrsening Renal Function in Decompensated Heart Failure

NCT ID: NCT01140399

Last Updated: 2017-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2017-04-30

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

Conditions

Acute Decompensated Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Infusional drug treatment

Diuretics or diuretics plus fixed low dose dopamine infusion

Group Type: ACTIVE_COMPARATOR

Furosemide or Furosemide and Dopamine

Intervention Type: DRUG

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.

Ultrafiltration

Device: Ultrafiltration appliance Sessions of 8 h UF are conducted on 2 subsequent days in the first 48 hours after randomization; a third session is performed on day 3 in case of persistent congestion

Group Type: EXPERIMENTAL

Ultrafiltration

Intervention Type: DEVICE

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

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Associazione Nazionale Medici Cardiologi Ospedalieri

OTHER

Sponsor Role: collaborator

Niguarda Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabrizio Oliva, MD

Role: STUDY_CHAIR

Heart Failure Heart Transplant Program, Cardiovascular Department, Niguarda Hospital, Milan, Italy

Antonio Santoro, MD

Role: STUDY_CHAIR

Department of Nephrology, Dialysis and Hypertension, Sant'Orsola Malpighi Hospital, Bologna, Italy

Locations

Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge

Cassano Murge, Bari, Italy

Ospedale Civile di Legnano Cardiology

Legnano, Milano, Italy

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

Ospedale SS Annunziata Cardiology

Cosenza, , Italy

Azienda Istituti Ospitalieri di Cremona Cardiology

Cremona, , Italy

Centro Cardiologico Monzino, I.R.C.C.S. Cardiology Intensive Care

Milan, , Italy

Azienda Ospedaliera Niguarda - Heart Failure and Heart Transplant Program

Milan, , Italy

Ospedale Guglielmo da Saliceto Cardiology Department

Piacenza, , Italy

AO Verona Ospedale Civile Maggiore Cardiology Unit

Verona, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 35061249 (View on PubMed)

Other Identifiers

FO001

Identifier Type: -

Identifier Source: secondary_id

EudraCT code 2009-014

Identifier Type: -

Identifier Source: org_study_id