Global rEgistry on decongestioN Therapy Using Less invasivE UltraFiltration

Acute Heart Failure Clinical Trial

— GENTLE-UF  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02769351
• Other study ID #: UF-HF-01-INT
• Secondary ID: DRKS00009836
• Status: Terminated
• Start date: December 3, 2015
• Est. completion date: March 4, 2019

Study information

• Verified date: April 2021
• Source: Fresenius Medical Care Deutschland GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 104
• Est. completion date: March 4, 2019
• Est. primary completion date: March 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Heart Failure
• Cardiac Decompensation
• Heart Failure
• Volume Overload

Intervention

Device:
• periph. minimal invasive ultrafiltration
ultrafiltration via a peripheral single-needle

Locations

Country	Name	City	State
Germany	Uniklinik RWTH Aachen	Aachen	North Rhine-Westphalia
Germany	Helios Klinik Attendorn	Attendorn	Nordrhein-Westfalen
Germany	Helios Klinikum Berlin Buch	Berlin
Germany	Städtisches Klinikum Braunschweig	Braunschweig	Niedersachsen
Germany	Helios Klinikum Duisburg	Duisburg	North Rhine-Westphalia
Germany	HELIOS Klinikum Erfurt	Erfurt	Thueringen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden Württemberg
Germany	Helios Klinikum Hildesheim	Hildesheim	Niedersachsen
Germany	Helios Klinik für Herzchirurgie GmbH Karlsruhe	Karlsruhe	Baden- Württemberg
Germany	Universitätsklinikum Mannheim	Mannheim	Baden-Württemberg
Germany	Klinikum Stuttgart	Stuttgart	Baden Württemberg
Sweden	Falun Hospital	Falun
Sweden	SUS Skanes University Hosptal	Malmö
Sweden	University Hospital Örebro	Örebro
Sweden	Danderyd University Hospital	Stockholm
Sweden	Karolinska University Hospital	Stockholm
Sweden	Uppsala University Hospital	Uppsala
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	UniversitätsSpital Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Fresenius Medical Care Deutschland GmbH

Countries where clinical trial is conducted

Germany,  Sweden,  Switzerland, 

References & Publications (2)

McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik 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. Erratum in: Eur J Heart Fail. 2013 Mar;15(3):361-2. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)