Acute Decompensated Heart FailurePhase 4REWORD-HFNCT01140399
REWORD-HF REverse WOrsening Renal Function in Decompensated Heart Failure
A Phase 4 study testing Furosemide or Furosemide and Dopamine and Ultrafiltration in people with Acute Decompensated Heart Failure, run by Niguarda Hospital at 16 sites in Italy.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Decompensated Heart Failure
- What is being tested?
- Furosemide or Furosemide and Dopamine and Ultrafiltration
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 16 sitesItaly
- Study dates
- Feb 2011to Apr 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Italy16 sites
Ospedali Riuniti di Ancona Cardiology Presidio Lancisi
Ancona, 60020
Ospedali Riuniti di Bergamo - Cardiovascular Medicine
Bergamo, 24128
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Cardiology Unit
Bologna, 40138
Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi - Nefrology,Dialysis and Hypertension Unit
Bologna, 40138
Fondazione S. Maugeri. IRCCS Istituto di Cassano Murge
Cassano Murge, Bari
Azienda Ospedaliera Sant'Anna - Cardiology
Como, 22100
Ospedale SS Annunziata Cardiology
Cosenza, 87100
Azienda Istituti Ospitalieri di Cremona Cardiology
Cremona, 26100
Ospedale Civile di Legnano Cardiology
Legnano, Milano, 20025
Centro Cardiologico Monzino, I.R.C.C.S. Cardiology Intensive Care
Milan, 20138
Azienda Ospedaliera Niguarda - Heart Failure and Heart Transplant Program
Milan, 20162
Azienda Ospedaliera S. Gerardo Heart Failure and Cardiomyopathy Clinic
Monza, Monza Brianza, 20052
Gruppo Policlinico di Monza Clinical Cardiology and Heart Failure Unit - Cardiology Department
Monza, Monza Brianza, 20052
Ospedale Guglielmo da Saliceto Cardiology Department
Piacenza, 29100
Istituto Clinico Humanitas - IRCCS Clinical Cardiology Cardiovascular Department
Rozzano, Milano, 20089
AO Verona Ospedale Civile Maggiore Cardiology Unit
Verona, 37126
About this study
Official title: Impact of Different Therapeutic Approaches in Patients With Cardiorenal Syndrome in the Setting of Acute Decompensated Congestive Heart Failure (ADCHF)
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
Read the 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
- Being tested
- Furosemide or Furosemide and Dopamine, Ultrafiltration
- Keywords
- 1 Acute Decompensated Heart Failure, 2 Cardiorenal Syndrome, 3 Ultrafiltration, 4 Dopamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide or Furosemide and DopamineDrug
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.
UltrafiltrationDevice
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
| Study group | Role | What they receive |
|---|---|---|
| Infusional drug treatment | Active comparator | Diuretics or diuretics plus fixed low dose dopamine infusion Receives: Drug: Furosemide or Furosemide and Dopamine |
| Ultrafiltration | Experimental | 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 Receives: Device: Ultrafiltration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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 (11)
Changes in the dyspnea Likert scale
Measured: Measured at day 4, at day 10, at day 90 vs baseline
Changes in modified RIFLE (AKIN) stage
Measured: Measured at day 4 vs baseline
Length of stay during index admission
Measured: Measured at average day 10
Occurrence of major adverse events
All cause mortality, hospital readmission and unscheduled office and emergency department visits for ADCHF
Measured: Measured at day 90
Days spent alive and out of hospital (DAOH) within 90 days
Sum of days spent alive and out of hospital
Measured: Measured at day 90
BNP changes
Changes in BNP at specified times VS baseline
Measured: 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
Measured: Measured at day -1, at day 0 and day 4
Changes in Cystatin C (CysC)
Changes in Cystatin C (CysC) at specified times VS baseline
Measured: Measured at day 0, day 4, day 10 and day 90
Treatment-related adverse events
Bleeding, thrombosis, clotting, infection
Measured: Measured at day 4
Adverse changes in blood pressure, heart rate and rhythm
Hypotension (< 90 mmHg), tachycardia (> 110 bpm) arrhythmias
Measured: Measured at day 4
Adverse changes in lab parameters
Hyper-Azotemia (>180 mg/dl), hyper-kaliemia (6.5 mEq/l), hemoconcentration (hematocrit >45%)
Measured: Measured at day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2010 (estimated)
- Study startFeb 2011
- Primary completionJun 2011
- Study completionApr 2017
Why it stopped: insufficient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Decompensated Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Associazione Nazionale Medici Cardiologi Ospedalieri
- Responsible party
- Sponsor
- Investigators
- Fabrizio Oliva, MD, Study chair, Heart Failure Heart Transplant Program, Cardiovascular Department, Niguarda Hospital, Milan, ItalyAntonio Santoro, MD, Study chair, Department of Nephrology, Dialysis and Hypertension, Sant'Orsola Malpighi Hospital, Bologna, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01140399
- Sponsor's protocol ID
- EudraCT code 2009-014
- Other IDs
- FO001
- Acronym
- REWORD-HF
- Status last verified
- Apr 2017
- First submitted
- 7 Jun 2010
- Last updated
- 10 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 35061249
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Different Therapeutic Approaches in Patients With Cardiorenal Syndrome in the Setting of Acute Decompensated Congestive Heart Failure (ADCHF)
- ClinicalTrials.gov ID
- NCT01140399
- Acronym / sponsor ID
- REWORD-HF / EudraCT code 2009-014
- Conditions
- Acute Decompensated Heart Failure
- Keywords
- 1 Acute Decompensated Heart Failure, 2 Cardiorenal Syndrome, 3 Ultrafiltration, 4 Dopamine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient enrollment
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Collaborators
- Associazione Nazionale Medici Cardiologi Ospedalieri
- Study start
- Feb 2011 (actual)
- Primary completion
- Jun 2011 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 9 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infusional drug treatment | Active comparator | Drug: Furosemide or Furosemide and DopamineDiuretics or diuretics plus fixed low dose dopamine infusion |
| Ultrafiltration | Experimental | Device: UltrafiltrationDevice: 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Furosemide or Furosemide and DopaminePatients 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. | Drug | Infusional drug treatment |
| UltrafiltrationAll 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 | Device | Ultrafiltration |
Primary outcome
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
Changes in a score derived by summing up changes in dyspnea, weight loss, glomerular filtration rate (GFR), brain natriuretic peptide (BNP)
11 secondary outcomes
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
Time frame: Measured at day 90
Days spent alive and out of hospital (DAOH) within 90 days
Time frame: Measured at day 90
BNP changes
Time frame: Measured at day 0, at day 4, at 10 and day 90
Changes in neutrophil gelatinase associated lipocalin (NGAL)
Time frame: Measured at day -1, at day 0 and day 4
Changes in Cystatin C (CysC)
Time frame: Measured at day 0, day 4, day 10 and day 90
Treatment-related adverse events
Time frame: Measured at day 4
Adverse changes in blood pressure, heart rate and rhythm
Time frame: Measured at day 4
Adverse changes in lab parameters
Time frame: Measured at day 4
Results and safety
The study was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2017.
- Derived from this study: PubMed 35061249Srivastava 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fabrizio Oliva, MD study chair
Heart Failure Heart Transplant Program, Cardiovascular Department, Niguarda Hospital, Milan, Italy
Antonio Santoro, MD study chair
Department of Nephrology, Dialysis and Hypertension, Sant'Orsola Malpighi Hospital, Bologna, Italy
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Furosemide or Furosemide and Dopamine and Ultrafiltration in people with Acute Decompensated Heart Failure, run by Niguarda Hospital at 16 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01140399, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2017.