Low recruitment

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).

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.

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

Of 44 randomized patients, 37 were included in the safety and full analysis set (SAS/ FAS).

Per patient adverse events were collected from signed informed consent until max 30 days after last clinical Investigation visit.

Adverse Event Definition and Collection has been according to ISO 14 155 "Clinical investigation of medical devices for human subjects - Good clinical practice."

Due to the premature termination of the study and a resulting sample size of 37 patients in both analyses sets no statistical testing for any study endpoint has been applied. All study objectives were analyzed purely descriptively, continuous data with sample statistics, categorical data by frequency tables.