REWORD-HF REverse WOrsening Renal Function in Decompensated Heart Failure

This study has suspended participant recruitment.
(insufficient enrollment)
Sponsor:
Collaborator:
Associazione Nazionale Medici Cardiologi Ospedalieri
Information provided by (Responsible Party):
Niguarda Hospital
ClinicalTrials.gov Identifier:
NCT01140399
First received: June 7, 2010
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Acute Decompensated Heart Failure
Drug: Furosemide or Furosemide and Dopamine
Device: Ultrafiltration
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Different Therapeutic Approaches in Patients With Cardiorenal Syndrome in the Setting of Acute Decompensated Congestive Heart Failure (ADCHF)

Resource links provided by NLM:


Further study details as provided by Niguarda Hospital:

Primary Outcome Measures:
  • Changes in a composite clinical-lab score [ 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 ] [ Designated as safety issue: No ]
    Changes in a score derived by summing up changes in dyspnea, weight loss, glomerular filtration rate (GFR), brain natriuretic peptide (BNP)


Secondary Outcome Measures:
  • Changes in the dyspnea Likert scale [ Time Frame: Measured at day 4, at day 10, at day 90 vs baseline ] [ Designated as safety issue: No ]
  • Changes in modified RIFLE (AKIN) stage [ Time Frame: Measured at day 4 vs baseline ] [ Designated as safety issue: Yes ]
  • Length of stay during index admission [ Time Frame: Measured at average day 10 ] [ Designated as safety issue: Yes ]
  • Occurrence of major adverse events [ Time Frame: Measured at day 90 ] [ Designated as safety issue: Yes ]
    All cause mortality, hospital readmission and unscheduled office and emergency department visits for ADCHF

  • Days spent alive and out of hospital (DAOH) within 90 days [ Time Frame: Measured at day 90 ] [ Designated as safety issue: Yes ]
    Sum of days spent alive and out of hospital

  • BNP changes [ Time Frame: Measured at day 0, at day 4, at 10 and day 90 ] [ Designated as safety issue: No ]
    Changes in BNP at specified times VS baseline

  • Changes in neutrophil gelatinase associated lipocalin (NGAL) [ Time Frame: Measured at day -1, at day 0 and day 4 ] [ Designated as safety issue: No ]
    Changes in NGAL at specified times VS screening

  • Changes in Cystatin C (CysC) [ Time Frame: Measured at day 0, day 4, day 10 and day 90 ] [ Designated as safety issue: No ]
    Changes in Cystatin C (CysC) at specified times VS baseline

  • Treatment-related adverse events [ Time Frame: Measured at day 4 ] [ Designated as safety issue: Yes ]
    Bleeding, thrombosis, clotting, infection

  • Adverse changes in blood pressure, heart rate and rhythm [ Time Frame: Measured at day 4 ] [ Designated as safety issue: Yes ]
    Hypotension (< 90 mmHg), tachycardia (> 110 bpm) arrhythmias

  • Adverse changes in lab parameters [ Time Frame: Measured at day 4 ] [ Designated as safety issue: Yes ]
    Hyper-Azotemia (>180 mg/dl), hyper-kaliemia (6.5 mEq/l), hemoconcentration (hematocrit >45%)


Estimated Enrollment: 186
Study Start Date: February 2011
Estimated Study Completion Date: May 2014
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Infusional drug treatment
Diuretics or diuretics plus fixed low dose dopamine infusion
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.
Experimental: 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
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


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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01140399

Locations
Italy
Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge
Cassano Murge, Bari, Italy
Ospedale Civile di Legnano Cardiology
Legnano, Milano, Italy, 20025
Istituto Clinico Humanitas - IRCCS Clinical Cardiology Cardiovascular Department
Rozzano, Milano, Italy, 20089
Azienda Ospedaliera S. Gerardo Heart Failure and Cardiomyopathy Clinic
Monza, Monza Brianza, Italy, 20052
Gruppo Policlinico di Monza Clinical Cardiology and Heart Failure Unit - Cardiology Department
Monza, Monza Brianza, Italy, 20052
Ospedali Riuniti di Ancona Cardiology Presidio Lancisi
Ancona, Italy, 60020
Ospedali Riuniti di Bergamo - Cardiovascular Medicine
Bergamo, Italy, 24128
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Nefrology,Dialysis and Hypertension Unit
Bologna, Italy, 40138
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Cardiology Unit
Bologna, Italy, 40138
Azienda Ospedaliera Sant'Anna - Cardiology
Como, Italy, 22100
Ospedale SS Annunziata Cardiology
Cosenza, Italy, 87100
Azienda Istituti Ospitalieri di Cremona Cardiology
Cremona, Italy, 26100
Azienda Ospedaliera Niguarda - Heart Failure and Heart Transplant Program
Milano, Italy, 20162
Centro Cardiologico Monzino, I.R.C.C.S. Cardiology Intensive Care
Milano, Italy, 20138
Ospedale Guglielmo da Saliceto Cardiology Department
Piacenza, Italy, 29100
AO Verona Ospedale Civile Maggiore Cardiology Unit
Verona, Italy, 37126
Sponsors and Collaborators
Niguarda Hospital
Associazione Nazionale Medici Cardiologi Ospedalieri
Investigators
Study Chair: Fabrizio Oliva, MD Heart Failure Heart Transplant Program, Cardiovascular Department, Niguarda Hospital, Milan, Italy
Study Chair: Antonio Santoro, MD Department of Nephrology, Dialysis and Hypertension, Sant'Orsola Malpighi Hospital, Bologna, Italy
  More Information

No publications provided

Responsible Party: Niguarda Hospital
ClinicalTrials.gov Identifier: NCT01140399     History of Changes
Other Study ID Numbers: EudraCT code 2009-014, FO001
Study First Received: June 7, 2010
Last Updated: May 19, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Niguarda Hospital:
1 Acute Decompensated Heart Failure
2 Cardiorenal Syndrome
3 Ultrafiltration
4 Dopamine

Additional relevant MeSH terms:
Cardio-Renal Syndrome
Heart Failure
Cardiovascular Diseases
Heart Diseases
Kidney Diseases
Renal Insufficiency
Urologic Diseases
Dopamine
Dopamine Agents
Furosemide
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Diuretics
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sodium Potassium Chloride Symporter Inhibitors
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014