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Ultrafiltration Versus Medical Therapies in the Management of the Cardio Renal Syndrome (UF-CARE)

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ClinicalTrials.gov Identifier: NCT02846337
Recruitment Status : Recruiting
First Posted : July 27, 2016
Last Update Posted : October 8, 2018
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Cardio-renal Syndrome Procedure: ULTRAFILTRATION Procedure: ENHANCED MEDICAL TREATMENT Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 154 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Ultrafiltration Versus Medical Therapies in the Management of the Cardio Renal Syndrome
Actual Study Start Date : March 31, 2017
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2021

Arm Intervention/treatment
Experimental: 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
Procedure: ULTRAFILTRATION

Peritoneal dialysis: at least one daily contact, 5 days a week minimum, with a hypertonic solution. Le number of contact et the stasis duration will be decided by the practitioner.

Hemodialysis: at least one hemodialysis per week, one hemofiltration and/or hemodiafiltration per week, and at least 2 liter of ultrafiltrate extraction per week. In case of serious interdialytic weight gain, and/or hemodynamic unsteadiness, sessions can be up to 6 per weeks. Sessions duration will be adjusted to the needful ultrafiltrate and hemodynamic tolerance.

Isolated ultrafiltration: at least once a week, and includes an extraction of minimum 2 liter ultrafiltrate in less than 4 hours. It could be done, according to routines and department capacity, on a hemodialysis generator, plasmatic exchange generator, or mobile ultrafiltration device.


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.
Procedure: ENHANCED MEDICAL TREATMENT
  • Close cardiologic and nephrologic follow-up, minimum 4 times a year, This incidence matches the heart failure, and chronic kidney failure care guidance for our sample
  • Medical care adjustment in order to apply European and American guidance for chronic heart failure care
  • Hydric, caloric, peptic and sodium input evaluation by a dietician, and adjustment if needed
  • Physical rehabilitation suggestions by a physiologist
  • Evaluation of an interventional approach requirement, and implementation if needed (pacemaker, defibrillator, cardiac resynchronization, diagnosis and therapeutic coronary angiography, ventricular stimulator) according to European and American guidance.




Primary Outcome Measures :
  1. death and/or unscheduled hospitalization [ Time Frame: 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 :
  1. Survival [ Time Frame: 12 months ]
    number of days spent alive and not hospitalized

  2. Survival [ Time Frame: 12 months ]
    Intervention effect on one-year overall survival

  3. Hospitalization for acute decompensated heart failure [ Time Frame: 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.

  4. Change in NYHA classification [ Time Frame: randomization day and 12 months post randomization. ]
    New York Health Association - Measurement scale to classify heart failure in 4 stages (stage 1 ; no symptoms)

  5. Change in 6MWT - Six-Minute Walk Test [ Time Frame: randomization day and 12 months post randomization. ]
    Six-minute walk test with an experimented physiologist. The distance in meters is retained.

  6. Change in MLwHF form [ Time Frame: 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

  7. Change in SF36 form [ Time Frame: 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.

  8. Death occurrence attributable to ultrafiltration technique [ Time Frame: up to 12 months post- randomization ]
    Safety: Death occurrence attributable to ultrafiltration technique, validated by an independent supervisory board, and any adverse event.

  9. Change in Brain Natriuretic Peptide and/or NT-Probating Natriuretic Peptide rate [ Time Frame: randomization day and 12 months post randomization ]
    Following biological features variation : Brain Natriuretic Peptide (BNP) and/or NT-ProBNP

  10. Change in total bilirubin rate [ Time Frame: randomization day, then 3, 6 and 12 months post randomization ]
    Following biological features variation : total bilirubin

  11. Change high-sensitivity T troponin rate [ Time Frame: randomization day and 12 months post randomization ]
    Following biological features variation : high-sensitivity T troponin

  12. Change in hemoglobin rate [ Time Frame: randomization day and 12 months post randomization ]
    Following biological features variation : hemoglobin

  13. Change in Left ventricular ejection fraction (LVEF) [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : left systolic function (LVEF)

  14. Change in Tricuspid annular plane systolic excursion (TAPSE) [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features :right systolic function (TAPSE)

  15. Change in tricuspid annular velocity [ Time Frame: 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

  16. Change in transmitral patterns classification [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : left diastolic function assessed by transmitral patterns classification

  17. Change in E/E' ratio [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : E/E'

  18. Change in pulmonary artery systolic pressure (PASP) [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : pulmonary artery systolic pressure (PASP)

  19. Change in Surface of the Left Atrium [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : Surface of the Left Atrium

  20. Change in right atrial pressure [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : Impact on right ventricular function assessed by right atrial pressure

  21. Change in cardiac index [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : cardiac index

  22. Change in cardiac flow [ Time Frame: randomization day and 12 months post randomization ]
    Following echocardiographic parameters features : cardiac flow



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02846337


Contacts
Contact: Laurent JUILLARD, Pr (0)472 110 159 ext +33 laurent.juillard@chu-lyon.fr
Contact: Laurent MAGAUD (0)472 112 805 ext +33 laurent.magaud@chu-lyon.fr

Locations
France
Hospices Civils de Lyon, Hôpital E Herriot, Service de néphrologie, 5 place d'Arsonval Recruiting
Lyon, Rhones Alpes, France, 69003
Contact: Laurent JUILLARD, Pr    (0)472 110 159 ext +33    laurent.juillard@chu-lyon.fr   
Contact: Laurent MAGAUD    (0)472 112 805 ext +33    laurent.magaud@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Laurent JUILLARD Hospices Civils de Lyon, 69002 LYON France

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02846337     History of Changes
Other Study ID Numbers: 69HCL15_0077
2016-A00518-43 ( Other Identifier: ID-RCB )
First Posted: July 27, 2016    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:
cardio-renal syndrome
hemodialysis
peritoneal dialysis
hemofiltration
composite endpoint

Additional relevant MeSH terms:
Syndrome
Cardio-Renal Syndrome
Disease
Pathologic Processes
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Heart Failure
Heart Diseases
Cardiovascular Diseases