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

• Sponsor: Fresenius Medical Care Deutschland GmbH (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02769351
• Collaborator: (none)
• Enrollment: 104
• Locations: 19
• Actual Duration (Months): 39
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Heart Failure; Cardiac Decompensation; Volume Overload	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 This individual method enables a precisely defined amount of fluid to be withdrawn.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 Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 104 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• 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
• Actual Study Start Date: Dec 3, 2015
• Actual Primary Completion Date: Mar 4, 2019
• Actual Study Completion Date: Mar 4, 2019

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Rehospitalisation (Yes/no) Due to Exacerbation of Heart Failure/Volume Overload of Other Origin [12 months]

   The number of rehospitalizations due to heart failure resp. volume overload has been measured as a clinical endpoint and analyzed based on the AP.

Secondary Outcome Measures

1. Significant Deterioration of Kidney Function - Creatinine [Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-9 months); Outpatient visit II ( 12 months)]

   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).

2. Significant Deterioration of Kidney Function - Urea [Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-6 months); Outpatient visit II (12 months)]

   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).

3. Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate) [Recruitment, Discharge from index hospitalization, Outapteint visit I (3-6 months), Outpatient visit II (12 months)]

   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).

4. Significant Deterioration of Kidney Function - Cystatin [recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months), Outpatient visit II (12 months)]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitätsklinikum Heidelberg	Heidelberg	Baden Württemberg	Germany	69120
2	Klinikum Stuttgart	Stuttgart	Baden Württemberg	Germany	70174
3	Helios Klinik für Herzchirurgie GmbH Karlsruhe	Karlsruhe	Baden- Württemberg	Germany	76185
4	Universitätsklinikum Mannheim	Mannheim	Baden-Württemberg	Germany	68167
5	Städtisches Klinikum Braunschweig	Braunschweig	Niedersachsen	Germany	38126
6	Helios Klinikum Hildesheim	Hildesheim	Niedersachsen	Germany	31135
7	Helios Klinik Attendorn	Attendorn	Nordrhein-Westfalen	Germany	57439
8	Uniklinik RWTH Aachen	Aachen	North Rhine-Westphalia	Germany	52074
9	Helios Klinikum Duisburg	Duisburg	North Rhine-Westphalia	Germany	47053
10	HELIOS Klinikum Erfurt	Erfurt	Thueringen	Germany	99089
11	Helios Klinikum Berlin Buch	Berlin		Germany	13125
12	Falun Hospital	Falun		Sweden	79182
13	SUS Skanes University Hosptal	Malmö		Sweden	20502
14	Karolinska University Hospital	Stockholm		Sweden	17176
15	Danderyd University Hospital	Stockholm		Sweden	18288
16	Uppsala University Hospital	Uppsala		Sweden	75185
17	University Hospital Örebro	Örebro		Sweden	70185
18	Kantonsspital Aarau	Aarau		Switzerland	5001
19	UniversitätsSpital Zurich	Zurich		Switzerland	8091

Sponsors and Collaborators

• Fresenius Medical Care Deutschland GmbH

Investigators

• Principal Investigator: Henning T Baberg, MD, Helios Klinikum Berlin Buch, Berlin

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 22, 2015

More Information

Publications

• 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.
• 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.

• Responsible Party: Fresenius Medical Care Deutschland GmbH
• ClinicalTrials.gov Identifier: NCT02769351
• Other Study ID Numbers: UF-HF-01-INT; DRKS00009836
• First Posted: May 11, 2016
• Last Update Posted: Aug 5, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Fresenius Medical Care Deutschland GmbH: volume overload; heart failure; cardiac decompensation; ultrafiltration
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Recruitment Details	Out of 104 patients recruited, 46 patients have been included in the safety population (SP; all patients included in analysis), and 44 patients have been included in the analysis population (AP; patients included in analysis with at least one ultrafiltration treatment).

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration periph. minimal invasive ultrafiltration: ultrafiltration via a peripheral single-needle
Period Title: Overall Study
STARTED	46
COMPLETED	4
NOT COMPLETED	42

Baseline Characteristics

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration periph. minimal invasive ultrafiltration: ultrafiltration via a peripheral single-needle
Overall Participants	44
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.71 (10.76)
Sex: Female, Male (Count of Participants)
Female	14 31.8%
Male	28 63.6%
Race and Ethnicity Not Collected (Count of Participants)
Weight, Continuous (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	90.19 (21.16)
Height, Continuous (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.93 (10.30)
Body-Mass-Index (BMI), Continuous (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.03 (5.10)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The outcome has been analyzed based on the AP (44 patients).

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration periph. minimal invasive ultrafiltration: ultrafiltration via a peripheral single-needle
Measure Participants	44
Rehospitalization due to Heart Failure	7
Rehospitalization due to other reasons	12

2. Secondary Outcome

Title	Significant Deterioration of Kidney Function - Creatinine
Description	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).
Time Frame	Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-9 months); Outpatient visit II ( 12 months)

Outcome Measure Data

Analysis Population Description

The outcome has been analyzed on the SP (46 patients). However, due to the observational character of the study, data are not always available for all patients. The actual number of patients with available data is depicted per time point.

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration
Measure Participants	46
Creatinine at Recruitment	208.30 (71.79)
Creatinine at Discharge from Index Hospitalization	180.66 (78.13)
Creatinine at Outpatient visit I	224.99 (162.7)
Creatinine at Outpatient visit II	430.31 (454.01)

3. Secondary Outcome

Title	Significant Deterioration of Kidney Function - Urea
Description	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).
Time Frame	Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-6 months); Outpatient visit II (12 months)

Outcome Measure Data

Analysis Population Description

The outcome has been analyzed on the SP (46 patients). However, due to the observational character of the study, data are not always available for all patients. The actual number of patients with available data is depicted per time point and variable.

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration
Measure Participants	46
Urea at Recruitment	21.7 (15.01)
Urea at Discharge from Index Hospitalization	51.67 (168.40)
Urea at Outpatient visit I	282.99 (457.51)

4. Secondary Outcome

Title	Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate)
Description	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).
Time Frame	Recruitment, Discharge from index hospitalization, Outapteint visit I (3-6 months), Outpatient visit II (12 months)

Outcome Measure Data

Analysis Population Description

The outcome has been analyzed on the SP (46 patients). However, due to the observational character of the study, data are not always available for all patients. The actual number of patients with available data is depicted per time point and variable.

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration
Measure Participants	46
eGFR at Recruitment	28.58 (15.56)
eGFR at Discharge from Index hositalization	37.82 (24.48)
eGFR at Outaptient visit I	36.19 (30.87)
eGFR at Outpatient visit II	41.52 (52.96)

5. Secondary Outcome

Title	Significant Deterioration of Kidney Function - Cystatin
Description	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).
Time Frame	recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months), Outpatient visit II (12 months)

Outcome Measure Data

Analysis Population Description

The outcome has been analyzed on the SP (46 patients). However, due to the observational character of the study, data are not always available for all patients. The actual number of patients with available data is depicted per time point and variable.

Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration
Measure Participants	46
Cystatin at Recruitment	2.26 (1.72)
Cystatin at Discharge from index Hospitalization	0.09 (0.13)
Cystatin at Outpatient visit II	6.99

Adverse Events

Time Frame	Adverse events were collected from signing the informed consent up to 12 month after recruitment.
Adverse Event Reporting Description	Adverse Event Definition has been done according to a form based on ISO 14155
Arm/Group Title	Periph. Minimal Invasive Ultrafiltration
Arm/Group Description	Patients with volume overload receiving ultrafiltration periph. minimal invasive ultrafiltration: ultrafiltration via a peripheral single-needle
All Cause Mortality
	Periph. Minimal Invasive Ultrafiltration
	Affected / at Risk (%)	# Events
Total	15/46 (32.6%)
Serious Adverse Events
	Periph. Minimal Invasive Ultrafiltration
	Affected / at Risk (%)	# Events
Total	22/46 (47.8%)
Cardiac disorders
Cardiac failure	9/46 (19.6%)	10
Cardiac failure chronic	2/46 (4.3%)	2
Cardiomyopathy	1/46 (2.2%)	1
General disorders
Death	4/46 (8.7%)	4
Immune system disorders
Demyelinating polyneuropathy	1/46 (2.2%)	1
Infections and infestations
Staphylococcal sepsis	2/46 (4.3%)	2
Injury, poisoning and procedural complications
Contusion	1/46 (2.2%)	1
Metabolism and nutrition disorders
Fluid retention	1/46 (2.2%)	1
Renal and urinary disorders
Chronic kidney disease	1/46 (2.2%)	1
Acute kidney injury	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/46 (2.2%)	1
Surgical and medical procedures
Hospitalisation	2/46 (4.3%)	2
Palliative care	1/46 (2.2%)	1
Catheter placement	1/46 (2.2%)	1
Peritoneal catheter insertion	1/46 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Periph. Minimal Invasive Ultrafiltration
	Affected / at Risk (%)	# Events
Total	4/46 (8.7%)
Cardiac disorders
Atrial fibrillation	1/46 (2.2%)	1
Product Issues
Thrombosis in device	1/46 (2.2%)	1
Surgical and medical procedures
Hospitalisation	2/46 (4.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.