Global rEgistry on decongestioN Therapy Using Less invasivE UltraFiltration (GENTLE-UF)

A Multicentre, Prospective Registry to Evaluate the Safety and Efficacy of Minimally Invasive Ultrafiltration Treatment and Its Effect on Symptoms and Rehospitalisation in Patients With Advanced Volume Overload

In patients with advanced volume overload, minimally invasive ultrafiltration treatment in the acute phase can have a positive effect on clinical outcome. The aim is to collect treatment data in the context of a prospective registry of the safety and performance of minimally invasive ultrafiltration. The data will be recorded via an electronic case report form (eCRF); the eCRF runs on a server located in Germany and complies with current data protection regulations. It is intended to include about 300-500 patients with advanced volume overload at a minimum of 10 sites. In addition, data on a disease management programme (in-body measurement and home monitoring) will be recorded in up to 40 of these patients. The treatment data from each patient will be recorded over 12 months. An interim analysis will be performed after 150 patients have been observed for 6 months. The knowledge about ultrafiltration in volume overload obtained from the registry, in some cases in combination with a disease management programme, is intended to improve the body of evidence. In addition, the data will be used for hypothesis generation.

Study Overview

• Status: Terminated
• Conditions: Acute Heart Failure; Volume Overload; Cardiac Decompensation
• Intervention / Treatment: Device: periph. minimal invasive ultrafiltration

Detailed Description

There may be various reasons why an increased accumulation of fluid occurs in tissue. The most common causes include heart failure, kidney failure or cirrhosis of the liver. In rare cases, oedema can develop following septicaemia. The usual treatment of oedema involves diuretics, i.e. water tablets, which remove excess fluid from the body and which can be administered either orally or intravenously. For some years now, it has also been possible to use ultrafiltration to treat oedema. This involves filtering and removing excess fluid from the blood. This individual method enables a precisely defined amount of fluid to be withdrawn. Access to the blood circulation is usually via a central venous catheter, as in acute dialysis. Current international treatment guidelines recommend that consideration should be given to ultrafiltration therapy in the context of treatment of diuretic-resistant volume overload (e.g. second- or third-line therapy for acute decompensated heart failure). There are, however, to date no clinical data on a combined treatment regimen of diuretics and supportive ultrafiltration. Accordingly, ultrafiltration may be included in clinical guidelines either only with a low level of evidence (e.g. IIb in the ACCF/AHA guidelines) or not at all (ESC guidelines). The main reasons for the limited body of evidence for ultrafiltration are, on the one hand, the invasive nature of the usual procedures (these usually require the insertion of a central venous catheter) and structural barriers in the health system (ultrafiltration is normally offered by nephrologists and not by cardiologists). With an increasing clinical need and limited medical alternatives, particularly in view of the frequently occurring diuretic resistance in heart failure, there is an urgent medical need to fill this gap in evaluation evidence. In the context of the registry, the CHIARA system, a minimally invasive (i.e. via a peripheral venous access) extracorporeal ultrafiltration system, is used for the treatment of decompensated volume overload. The CHIARA system has a CE mark for the intended purpose of ultrafiltration of the blood of patients suffering from heart failure, acute or chronic renal failure or excess body fluid. It is planned to use the medical device in connection with this intended purpose only. In participating hospitals, patients will be treated with this new treatment strategy of minimally invasive ultrafiltration treatment in support of diuretic drug therapy in the acute phase of volume overload. It is possible with the use of ultrafiltration therapy to control volume overload and reduce it on an individual basis, so that diuretics can be given sparingly and, as a consequence, diuretic resistance and a deterioration of renal function due to diuretic uptitration can be avoided.

• Study Type: Observational
• Enrollment (Actual): 104

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin Buch
  • Baden Württemberg
    • Heidelberg, Baden Württemberg, Germany, 69120
      • UniversitatsKlinikum Heidelberg
    • Stuttgart, Baden Württemberg, Germany, 70174
      • Klinikum Stuttgart
  • Baden- Württemberg
    • Karlsruhe, Baden- Württemberg, Germany, 76185
      • Helios Klinik für Herzchirurgie GmbH Karlsruhe
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167
      • Universitätsklinikum Mannheim
  • Niedersachsen
    • Braunschweig, Niedersachsen, Germany, 38126
      • Städtisches Klinikum Braunschweig
    • Hildesheim, Niedersachsen, Germany, 31135
      • Helios Klinikum Hildesheim
  • Nordrhein-Westfalen
    • Attendorn, Nordrhein-Westfalen, Germany, 57439
      • Helios Klinik Attendorn
  • North Rhine-Westphalia
    • Aachen, North Rhine-Westphalia, Germany, 52074
      • Uniklinik RWTH Aachen
    • Duisburg, North Rhine-Westphalia, Germany, 47053
      • Helios Klinikum Duisburg
  • Thueringen
    • Erfurt, Thueringen, Germany, 99089
      • Helios Klinikum Erfurt
• Sweden
  • Falun, Sweden, 79182
    • Falun hospital
  • Malmö, Sweden, 20502
    • SUS Skanes University Hosptal
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital
  • Stockholm, Sweden, 18288
    • Danderyd University Hospital
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital
  • Örebro, Sweden, 70185
    • University hospital Örebro
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
  • Zurich, Switzerland, 8091
    • Universitätsspital Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients treated with minimally invasive ultrafiltration in support of diuretic drug therapy in the acute phase of volume overload.

Description

Inclusion Criteria:

• ≥18 years
• Inpatient-treated patients with acute volume overload, preferably in association with cardiac decompensation with signs of incipient diuretic resistance (lack of increase in urine output despite significant escalation of diuretic therapy; e.g. ≥80 mg furosemide / 24 h or less than 1375 mL urine output/40 mg furosemide per 24 h or equivalent dose of other loop diuretics [established clinically or from the medical history])
• New York Association Functional Class (NYHA) III-IV at inclusion
• Systolic or diastolic cardiac dysfunction (HF-REF or HF-PEF)
• Adequate venous access (preferably peripheral arm vein) allowing a flow rate ≥ 60 mL / min
• Written consent to the use of data in the registry (where necessary, by a legal guardian).

Exclusion Criteria:

• Contraindication to anticoagulation (e.g. known heparin-induced thrombocytopenia, severe bleeding)
• Terminal renal failure (stage V, GFR <15 mL)
• Cardiogenic shock, e.g. in association with acute coronary syndrome (ACS)
• Other diseases or factors that, in the study doctor's opinion, constitute a potential contraindication to ultrafiltration
• Pregnant women, women in labour, breast-feeding women or women of childbearing potential, who are without adequate contraception or are planning a family. NB: a pregnancy test is performed systematically in women of childbearing age and the patient is not included in the event of pregnancy (positive test). It is absolutely essential that women, who have a negative test and who are included in the study, have an effective contraception.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
periph. minimal invasive ultrafiltration; Patients with volume overload receiving ultrafiltration	Device: periph. minimal invasive ultrafiltration; ultrafiltration via a peripheral single-needle; Other Names: ultrafiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rehospitalisation (Yes/no) Due to Exacerbation of Heart Failure/Volume Overload of Other Origin	The number of rehospitalizations due to heart failure resp. volume overload has been measured as a clinical endpoint and analyzed based on the AP.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Significant Deterioration of Kidney Function - Creatinine	Significant deterioration of kidney function has been measured as a safety endpoint and analyzed based on the SP. The variables have been measured at recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months) and Outpatient visit II (12 months).	Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-9 months); Outpatient visit II ( 12 months)
Significant Deterioration of Kidney Function - Urea	Significant deterioration of kidney function has been measured as a safety endpoint and analyzed based on the SP. The variables have been measured at recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months) and Outpatient visit II (12 months).	Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-6 months); Outpatient visit II (12 months)
Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate)	Significant deterioration of kidney function has been measured as a safety endpoint and analyzed based on the SP. The variables have been measured at recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months) and Outpatient visit II (12 months).	Recruitment, Discharge from index hospitalization, Outapteint visit I (3-6 months), Outpatient visit II (12 months)
Significant Deterioration of Kidney Function - Cystatin	Significant deterioration of kidney function has been measured as a safety endpoint and analyzed based on the SP. The variables have been measured at recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months) and Outpatient visit II (12 months).	recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months), Outpatient visit II (12 months)

Collaborators and Investigators

• Sponsor: Fresenius Medical Care Deutschland GmbH
• Investigators: Principal Investigator: Henning T Baberg, MD, Helios Klinikum Berlin Buch, Berlin

Publications and helpful links

General Publications

• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239. doi: 10.1016/j.jacc.2013.05.019. Epub 2013 Jun 5. No abstract available.
• McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology; Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P; ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012 Aug;14(8):803-69. doi: 10.1093/eurjhf/hfs105. No abstract available. Erratum In: Eur J Heart Fail. 2013 Mar;15(3):361-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 3, 2015
• Primary Completion (ACTUAL): March 4, 2019
• Study Completion (ACTUAL): March 4, 2019

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (ESTIMATE): May 11, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: heart failure; ultrafiltration; volume overload; cardiac decompensation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: UF-HF-01-INT; DRKS00009836 (REGISTRY: DRKS: German Clinical Trials Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Overall results will be published. Individual participant data will not be made available.