Acute Heart Failure, Heart Failure
Conditions
Keywords
Cardio-Renal Syndrome type 1, Acutely decompensated chronic heart failure, Ultrafiltration
Brief summary
This study evaluates whether tailored, peripheral ultrafiltration complementary to low-dose diuretics is associated with a reduction in cardiovascular mortality in 90 days after randomization and heart failure events in 90 days after discharge than usual care including stepped intravenous diuretics in acutely decompensated chronic heart failure with fluid overload (not fully responsive to diuretic therapy).
Detailed description
The study will evaluate whether stepped, peripheral ultrafiltration complementary to low-dose diuretics influences 90-day clinical outcomes compared to usual care including intravenous diuretics in symptomatic heart failure patients with persistent congestion. Hospitalized subjects will be randomly assigned to receive either a tailored, peripheral ultrafiltration approach complementary to intravenous low-dose diuretics and other guideline-directed medical therapy OR high-dose diuretic therapy and other Guideline-directed medical therapy.
Interventions
DEVICECHIARA-System
Treatment with veno-venous ultrafiltration (CHIARA-System) complementary to low-dose diuretic therapy according to treatment algorithm. 1-7 Ultrafiltration sessions (6-10h/session, number of sessions depending on clinical assessment) for at least 1-2 consecutive days and a maximum of 7 days.
OTHERUsual care IV diuretics
Guideline-directed therapy including IV loop diuretics (according to treatment algorithm)
Sponsors
Fresenius Medical Care Deutschland GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, prospective, randomized, parallel-group, controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General: Informed consent signed and dated by study patient and investigator/authorised physician * Minimum age of 18 years * Ability to understand the nature and requirements of the study Study-specific: * Heart failure patients with preserved, mid-range or reduced ejection fraction (confirmed according to the current definitions of heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF) requiring echocardiographic assessment within the prior 12 months) who are admitted to the hospital due to signs/symptoms of congestion (left- or right sided) * On regularly scheduled oral loop diuretics prior to admission * Patients who have received IV loop diuretics for decongestion within 24 hours after hospital admission and prior to screening. The dosages are administered according to clinical judgment.\*\* (\*\*This inclusion criterion was changed with CIP amendment; in former version 3.0 it read After pre-screening and prior to final screening for eligibility, patients who have received two boluses of IV loop diuretics (Dose according to the Furosemide-Low Intensification, Q12 hour bolus arm of the DOSE trial)) * Symptoms of congestion and clinical evidence at the time of final screening for eligibility: * Fluid overload manifested by at least 2 of the following: 1. Pitting edema ≥2+ of the lower extremities 2. Jugular venous pressure \>8 cm H2O 3. Pulmonary congestion or pleural effusion on chest x-ray 4. Paroxysmal nocturnal dyspnea or ≥2- pillow orthopnea 5. Respiration rate ≥20 per minute * Additional objective documentation of congestion: Lung or inferior vena cava ultrasound, chest x-ray or elevated filling pressures, if available, at the time of randomization (optional)
Exclusion criteria
General: * Any condition which could interfere with the patient's ability to comply with the study * In case of female patients, pregnancy or lactation period * Participation in an interventional clinical study during the preceding 30 days * Previous participation in the same study * Unwillingness or inability to complete follow up * Active drug or alcohol abuse (smoking allowed) Study-specific: * Acute coronary syndrome requiring intervention during index hospitalization * Severe renal dysfunction requiring renal replacement therapy * Systolic blood pressure \< 90 mmHg at the time of randomization * Pulmonary hypertension not secondary to left heart disease * Pulmonary disease thought to be primarily responsible for symptoms * Contraindication to systemic anticoagulation * Severe concomitant disease expected to prolong hospitalization or to cause death in ≤ 90 days * Sepsis * Severe uncorrected valvular stenosis at the time of randomization * Active myocarditis * Hypertrophic obstructive cardiomyopathy * Constrictive pericarditis or restrictive cardiomyopathy * Liver cirrhosis due to primary liver disease\* (\*Restriction due to primary liver disease was present after amendment in study protocol version 5.0 but not in version 3.0) * Known infection with human immunodeficiency virus (HIV) or active hepatitis C * Previous solid organ transplant * Presence or requirement for mechanical respiratory support * Presence or requirement of a mechanical circulatory support device * Need for IV positive inotropic agents at the time of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart Failure (HF) Event | in 90 days after discharge | Heart failure hospitalization or unscheduled outpatient or emergency department treatment with IV loop diuretics or ultrafiltration. |
| Cardiovascular Death up to 90 Days After Randomization. | in 90 days after discharge | The rationale for the follow up time period of 90 days is that death rates reported in previous acute HF trials indicate that mortality seems to become linear after \ 60-90 days post discharge Collection for Cardiovascular Trials initiative definition of cardiovascular death includes death resulting from an acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, and death due to other cardiovascular causes |
Countries
Germany, Sweden
Participant flow
Recruitment details
Of 62 enrolled patients, 44 were randomized to treatment. 37 patients were included in the safety and full analysis set (SAF/FAS)
Participants by arm
| Arm | Count |
|---|---|
| Ultrafiltration Group Veno-venous ultrafiltration (CHIARA-System) complementary to low-dose diuretic therapy according to treatment algorithm.
CHIARA-System: Treatment with veno-venous ultrafiltration (CHIARA-System) complementary to low-dose diuretic therapy according to treatment algorithm. 1-7 Ultrafiltration sessions (6-10h/session, number of sessions depending on clinical assessment) for at least 1-2 consecutive days and a maximum of 7 days. | 18 |
| Control Group (Usual Care IV Diuretics) Guideline-directed therapy including IV loop diuretics according to treatment algorithm.
Usual care IV diuretics: Guideline-directed therapy including IV loop diuretics (according to treatment algorithm) | 19 |
| Total | 37 |
Baseline characteristics
| Characteristic | Ultrafiltration Group | Control Group (Usual Care IV Diuretics) | Total |
|---|---|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 9.45 | 74.2 years STANDARD_DEVIATION 12.4 | 72.9 years STANDARD_DEVIATION 11 |
| Age, Customized ≥ 45 to <65 years | 6 Participants | 2 Participants | 8 Participants |
| Age, Customized <45 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized ≥65 years | 12 Participants | 16 Participants | 28 Participants |
| Body-Mass-Index (BMI) ≥18.5 to <25 kg/m^2 | 1 Participants | 4 Participants | 5 Participants |
| Body-Mass-Index (BMI) ≥25 to <30 kg/m^2 | 8 Participants | 4 Participants | 12 Participants |
| Body-Mass-Index (BMI) ≥30 to <35 | 1 Participants | 6 Participants | 7 Participants |
| Body-Mass-Index (BMI) ≥35 to <40 kg/m^2 | 2 Participants | 3 Participants | 5 Participants |
| Body-Mass-Index (BMI) ≥40 kg/m^2 | 6 Participants | 2 Participants | 8 Participants |
| Diastolic Blood Pressure (DBP) | 68.4 mmHg STANDARD_DEVIATION 10.62 | 70.4 mmHg STANDARD_DEVIATION 14.68 | 69.4 mmHg STANDARD_DEVIATION 12.73 |
| Heart rate | 73.2 bpm STANDARD_DEVIATION 20.32 | 71.9 bpm STANDARD_DEVIATION 14.57 | 72.5 bpm STANDARD_DEVIATION 17.28 |
| Height | 173.4 cm STANDARD_DEVIATION 7.8 | 172.3 cm STANDARD_DEVIATION 13.28 | 172.8 cm STANDARD_DEVIATION 10.83 |
| New York Heart Association (NYHA) Functional Classification Missing | 1 Participants | 0 Participants | 1 Participants |
| New York Heart Association (NYHA) Functional Classification NYHA I | 0 Participants | 0 Participants | 0 Participants |
| New York Heart Association (NYHA) Functional Classification NYHA II | 1 Participants | 0 Participants | 1 Participants |
| New York Heart Association (NYHA) Functional Classification NYHA III | 14 Participants | 14 Participants | 28 Participants |
| New York Heart Association (NYHA) Functional Classification NYHA IV | 2 Participants | 5 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
| Systolic Blood Pressure (SBP) | 117.6 mmHg STANDARD_DEVIATION 26.23 | 128.5 mmHg STANDARD_DEVIATION 29.84 | 123.2 mmHg STANDARD_DEVIATION 28.3 |
| Weight | 106.4 kg STANDARD_DEVIATION 33.17 | 95.6 kg STANDARD_DEVIATION 27.42 | 100.9 kg STANDARD_DEVIATION 30.42 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 18 | 2 / 19 |
| other Total, other adverse events | 12 / 18 | 14 / 19 |
| serious Total, serious adverse events | 15 / 18 | 13 / 19 |
Outcome results
Primary
Cardiovascular Death up to 90 Days After Randomization.
The rationale for the follow up time period of 90 days is that death rates reported in previous acute HF trials indicate that mortality seems to become linear after \ 60-90 days post discharge Collection for Cardiovascular Trials initiative definition of cardiovascular death includes death resulting from an acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, and death due to other cardiovascular causes
Time frame: in 90 days after discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ultrafiltration Group | Cardiovascular Death up to 90 Days After Randomization. | 4 Participants |
| Control Group (Usual Care IV Diuretics) | Cardiovascular Death up to 90 Days After Randomization. | 1 Participants |
Primary
Heart Failure (HF) Event
Heart failure hospitalization or unscheduled outpatient or emergency department treatment with IV loop diuretics or ultrafiltration.
Time frame: in 90 days after discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ultrafiltration Group | Heart Failure (HF) Event | 4 Participants |
| Control Group (Usual Care IV Diuretics) | Heart Failure (HF) Event | 4 Participants |