PURE-HF: Peripheral Ultrafiltration for the RElief From Congestion in Heart Failure

Not Applicable

Terminated

• Conditions: Heart Failure; Acute Heart Failure
• Interventions: Device: CHIARA-System; Other: Usual care IV diuretics

• Registration Number: NCT03161158
• Lead Sponsor: Fresenius Medical Care Deutschland GmbH

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.

Study Timeline

• Study First Submitted: 2017-05-02
• Study First Submitted QC: 2017-05-18
• Study First Posted: 2017-05-19
• Study Start: 2017-11-03
• Primary Completion: 2019-08-26
• Study Completion: 2019-08-26
• Status Verified: 2020-07
• Results First Submitted: 2020-12-16
• Results First Submitted QC: 2021-04-08
• Last Update Submitted: 2021-04-08
• Results First Posted: 2021-05-05
• Last Update Posted: 2021-05-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 62

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ultrafiltration Group	CHIARA-System	Veno-venous ultrafiltration (CHIARA-System) complementary to low-dose diuretic therapy according to treatment algorithm.
Control group (Usual care IV diuretics)	Usual care IV diuretics	Guideline-directed therapy including IV loop diuretics according to treatment algorithm.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (11)

Universitätsklinikum Aachen (Med. Klinik II); 🇩🇪 Aachen, Germany

Helios Klinikum Duisburg; 🇩🇪 Duisburg, Germany

Helios Klinikum Erfurt GmbH; 🇩🇪 Erfurt, Germany

Helios Klinikum Hildesheim GmbH; 🇩🇪 Hildesheim, Germany

Medizinische Universitätsklinik, Innere Medizin III; 🇩🇪 Heidelberg, Germany

Klinikum Stuttgart, Klinik für Nieren-, Hochdruck- und Autoimmunerkrankungen; 🇩🇪 Stuttgart, Germany

Falun Hospital; 🇸🇪 Falun, Sweden

Danderyds University Hospital; 🇸🇪 Stockholm, Sweden

Karolinska University Hospital Huddinge, Department of Cardiology; 🇸🇪 Stockholm, Sweden

Uppsala University Hospital, Department of Cardiology; 🇸🇪 Uppsala, Sweden

Universitetssjukhuset Örebro, Hjärtsviktsmottagningen; 🇸🇪 Örebro, Sweden