Acute Heart Failure, Cardiac Decompensation, Volume Overload
Conditions
Keywords
volume overload, heart failure, cardiac decompensation, ultrafiltration
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.
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 This individual method enables a precisely defined amount of fluid to be withdrawn.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.
Interventions
DEVICEperiph. minimal invasive ultrafiltration
ultrafiltration via a peripheral single-needle
Sponsors
Fresenius Medical Care Deutschland GmbH
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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). |
Countries
Germany, Sweden, Switzerland
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).
Participants by arm
| Arm | Count |
|---|---|
| Periph. Minimal Invasive Ultrafiltration Patients with volume overload receiving ultrafiltration
periph. minimal invasive ultrafiltration: ultrafiltration via a peripheral single-needle | 44 |
| Total | 44 |
Baseline characteristics
| Characteristic | Periph. Minimal Invasive Ultrafiltration | — |
|---|---|---|
| Age, Continuous | 74.71 years STANDARD_DEVIATION 10.76 | — |
| Body-Mass-Index (BMI), Continuous | 30.03 kg/m^2 STANDARD_DEVIATION 5.1 | — |
| Height, Continuous | 171.93 cm STANDARD_DEVIATION 10.3 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 14 Participants | — |
| Sex: Female, Male Male | 28 Participants | — |
| Weight, Continuous | 90.19 kg STANDARD_DEVIATION 21.16 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 46 |
| other Total, other adverse events | 4 / 46 |
| serious Total, serious adverse events | 22 / 46 |
Outcome results
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.
Time frame: 12 months
Population: The outcome has been analyzed based on the AP (44 patients).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Periph. Minimal Invasive Ultrafiltration | Rehospitalisation (Yes/no) Due to Exacerbation of Heart Failure/Volume Overload of Other Origin | Rehospitalization due to Heart Failure | 7 Rehospitalizations |
| Periph. Minimal Invasive Ultrafiltration | Rehospitalisation (Yes/no) Due to Exacerbation of Heart Failure/Volume Overload of Other Origin | Rehospitalization due to other reasons | 12 Rehospitalizations |
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).
Time frame: Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-9 months); Outpatient visit II ( 12 months)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Creatinine | Creatinine at Recruitment | 208.30 mg/L | Standard Deviation 71.79 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Creatinine | Creatinine at Discharge from Index Hospitalization | 180.66 mg/L | Standard Deviation 78.13 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Creatinine | Creatinine at Outpatient visit I | 224.99 mg/L | Standard Deviation 162.7 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Creatinine | Creatinine at Outpatient visit II | 430.31 mg/L | Standard Deviation 454.01 |
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).
Time frame: recruitment, discharge from the index hospitalization, Outpatient visit I (3-9 months), Outpatient visit II (12 months)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Cystatin | Cystatin at Recruitment | 2.26 mg/mL | Standard Deviation 1.72 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Cystatin | Cystatin at Discharge from index Hospitalization | 0.09 mg/mL | Standard Deviation 0.13 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Cystatin | Cystatin at Outpatient visit II | 6.99 mg/mL | — |
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).
Time frame: Recruitment, Discharge from index hospitalization, Outapteint visit I (3-6 months), Outpatient visit II (12 months)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate) | eGFR at Recruitment | 28.58 mL/min*1.73^2 | Standard Deviation 15.56 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate) | eGFR at Discharge from Index hositalization | 37.82 mL/min*1.73^2 | Standard Deviation 24.48 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate) | eGFR at Outaptient visit I | 36.19 mL/min*1.73^2 | Standard Deviation 30.87 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - eGFR (Estimated Glomerular Filtration Rate) | eGFR at Outpatient visit II | 41.52 mL/min*1.73^2 | Standard Deviation 52.96 |
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).
Time frame: Recruitment; Discharge from Index Hospitalization; Outpatient visit I (3-6 months); Outpatient visit II (12 months)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Urea | Urea at Recruitment | 21.7 mg/dL | Standard Deviation 15.01 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Urea | Urea at Discharge from Index Hospitalization | 51.67 mg/dL | Standard Deviation 168.4 |
| Periph. Minimal Invasive Ultrafiltration | Significant Deterioration of Kidney Function - Urea | Urea at Outpatient visit I | 282.99 mg/dL | Standard Deviation 457.51 |