Ultrafiltration Versus Medical Therapies in the Management of the Cardio Renal Syndrome

Not Applicable

• Conditions: Cardio-renal Syndrome
• Interventions: Procedure: ULTRAFILTRATION; Procedure: ENHANCED MEDICAL TREATMENT

• Registration Number: NCT02846337
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Type 2 cardio renal syndrome is defined by the occurrence or the exacerbation of a kidney failure induced by a chronic heart failure. Sodium overload is one of the main causes leading to the occurrence or the exacerbation of this syndrome. Some patients have a massive sodium retention on which medications are not effective enough. These patients have no further therapeutic options because of the refractory congestion and a 3-months mortality rate around 15%, frequent rehospitalization (3-months rehospitalization rate at 71%) and an excessively impaired quality of life.

For those refractory heart failure with cardio renal syndrome, nephrology departments resort to non-medication sodium extraction (hemodialysis, peritoneal dialysis, isolated ultrafiltration). Between 2002 and 2008, 927 French patients would have start dialysis in this situation. In 2013, 174 patients start dialysis in 97 dialysis centers. French National Authority of Health recently published new Good Practice Guidance thereupon, strengthened by the increasing number of publications and the widespread use of this technique. There is therefore a consensus among professionals about the benefits of such a technique in those indications. However, bibliographical data are not strong enough to support a strong level of evidence. None of foresight strategies have been compared to others in a proper randomized controlled trial, and there is no clue about any suspected superiority from one strategy to another.

So far, the investigators propound invasive, expensive and not validated techniques to patients with functional and vital prognosis altered. The investigators think it's essential to prove the efficacy of such an approach. They wish to quantify those techniques impact on rehospitalization, with a consideration for the potential survival impact.

It seems unethical to evaluate separated techniques, taking in account that patients with severe heart failure will switch from one technique to another among their care. It is therefore crucial to validate benefits from an invasive procedure (hemodialysis, peritoneal dialysis, isolated ultrafiltration) compared to a medication-restricted care.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-07-22
• Study First Submitted QC: 2016-07-26
• Study First Posted: 2016-07-27
• Study Start: 2017-03-31
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-05
• Last Update Posted: 2018-10-09
• Primary Completion: 2021-09-30
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 154

Inclusion Criteria

• Severe heart failure with recurring congestive symptoms and at least one the following criteria :

  • At least 2 hospitalization > 24 hours for congestive symptoms among the 12 months before the inclusion, whose latest one was in the 6 months before the inclusion
  • Persistent congestive symptoms throughout 30 days (case history) before the randomization: dyspnea NYHA III or IV, lower limbs edema and/or ascites.

• Diuretic treatment with at least 250mg furosemide per day (or 6mg bumetanide)during at least 1 month

• Cardiac medical treatment enhanced by the European cardiology society guidance (except intolerance, and/or contraindication) and according to patient cardiologist.

• Non terminal kidney disease or failure : estimated glomerular filtration rate (GFR) (CKD-Epi formula) between 20 and 90 mL/min/1.73m² (or GFR estimated between 60 and 90 mL/min/1.73m² with proteinuria and/or hematuria) and urea rate under 50mmol/L

Read More

Exclusion Criteria

• Cardiogenic shock or situations that contraindicate the ultrafiltration technique elsewhere than shock room
• Patient who already had long course ultrafiltration for more than 3 months, or not available because of end-stage renal failure
• Biventricular pacemaker implementation, single or dual chamber pacemaker implementation, or defibrillator implementation up to 15 days before the inclusion
• Vasoactive drugs ambulatory treatment (dobutamine, dopamine, adrenalin, noradrenalin)
• General condition incompatible with any ultrafiltration techniques
• Age under 18
• Pregnant or lactating women
• Law-protected patients
• Patients that can't submit to the follow-up for geographical, social or mental reasons
• Unwillingness to be treated by ultrafiltration techniques
• Patients who don't belong to the national social security system, or similar system.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ULTRAFILTRATION	ULTRAFILTRATION	The ultrafiltration sodium-overload extraction will be chosen by the patient nephrologist and the patient himself (according to his comorbidities) among the following one: peritoneal dialysis (at least a daily contact), hemodialysis (\>1 session per week) or isolated ultrafiltration (\>1 session per week). Ultrafiltration technique could change throughout the care
ENHANCED MEDICAL TREATMENT	ENHANCED MEDICAL TREATMENT	The control group called "enhanced medical treatment" will not benefit of ultrafiltration (except refractory pulmonary edema, or terminal kidney failure requiring extra renal depuration). These situations will not be considered as protocol violation, because they are scientifically indicated for extra renal depuration.

Primary Outcome Measures

Name	Time	Method
death and/or unscheduled hospitalization	up to 12 months post-randomization	The primary outcome measure is a combined measure including death whatever the cause, and/or unscheduled hospitalization for acute decompensated heart failure. For each groups, deaths, cause and time of deaths will be recorded. Hospitalization date, duration, location, and reason will be recorded. The "hospitalization" setting and the "acute decompensated heart failure" setting will be endorsed by an event validation committee.

Secondary Outcome Measures

Name	Time	Method
Change in Surface of the Left Atrium	randomization day and 12 months post randomization	Following echocardiographic parameters features : Surface of the Left Atrium
Hospitalization for acute decompensated heart failure	up to 12 months post- randomization	Intervention effect on : * Period before first unscheduled hospitalization for acute decompensated heart failure; * Number and duration of hospitalizations for acute heart failure (scheduled or not) throughout the year; * Number and duration of unscheduled hospitalization for acute heart failure throughout the year.
Change in tricuspid annular velocity	randomization day and 12 months post randomization	Following echocardiographic parameters features : right systolic function assessed by tricuspid annular velocity measured with Pulsed Doppler tissue imaging
Change in hemoglobin rate	randomization day and 12 months post randomization	Following biological features variation : hemoglobin
Change in total bilirubin rate	randomization day, then 3, 6 and 12 months post randomization	Following biological features variation : total bilirubin
Change in Left ventricular ejection fraction (LVEF)	randomization day and 12 months post randomization	Following echocardiographic parameters features : left systolic function (LVEF)
Change in pulmonary artery systolic pressure (PASP)	randomization day and 12 months post randomization	Following echocardiographic parameters features : pulmonary artery systolic pressure (PASP)
Change in 6MWT - Six-Minute Walk Test	randomization day and 12 months post randomization.	Six-minute walk test with an experimented physiologist. The distance in meters is retained.
Death occurrence attributable to ultrafiltration technique	up to 12 months post- randomization	Safety: Death occurrence attributable to ultrafiltration technique, validated by an independent supervisory board, and any adverse event.
Change in Tricuspid annular plane systolic excursion (TAPSE)	randomization day and 12 months post randomization	Following echocardiographic parameters features :right systolic function (TAPSE)
Survival	12 months	Intervention effect on one-year overall survival
Change in NYHA classification	randomization day and 12 months post randomization.	New York Health Association - Measurement scale to classify heart failure in 4 stages (stage 1 ; no symptoms)
Change in MLwHF form	randomization day and 12 months post randomization.	Minnesota Living with Heart Failure - Quality of life self-administered survey focusing on heart failure symptoms (21 items with 1 : slightly to 5 : al lot) Safety issue? 0 Yes 1 No
Change in SF36 form	randomization day and 12 months post randomization.	Short Form 36 : Quality of life self-administered survey with 36 items about 8 dimensions including a physical and mental score.
Change in Brain Natriuretic Peptide and/or NT-Probating Natriuretic Peptide rate	randomization day and 12 months post randomization	Following biological features variation : Brain Natriuretic Peptide (BNP) and/or NT-ProBNP
Change high-sensitivity T troponin rate	randomization day and 12 months post randomization	Following biological features variation : high-sensitivity T troponin
Change in transmitral patterns classification	randomization day and 12 months post randomization	Following echocardiographic parameters features : left diastolic function assessed by transmitral patterns classification
Change in E/E' ratio	randomization day and 12 months post randomization	Following echocardiographic parameters features : E/E'
Change in right atrial pressure	randomization day and 12 months post randomization	Following echocardiographic parameters features : Impact on right ventricular function assessed by right atrial pressure
Change in cardiac index	randomization day and 12 months post randomization	Following echocardiographic parameters features : cardiac index
Change in cardiac flow	randomization day and 12 months post randomization	Following echocardiographic parameters features : cardiac flow

Trial Locations

Locations (1)

Hospices Civils de Lyon, Hôpital E Herriot, Service de néphrologie, 5 place d'Arsonval; 🇫🇷 Lyon, Rhones Alpes, France