Clinical trial NCT03499236: Reducing Lung CongestIon Symptoms in Advanced Heart Failure
Official title: RELIEVE-HF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure
Lead sponsor: V-Wave Ltd
Sponsor class: INDUSTRY
First posted: 2018-04-17
Enrollment: 605
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized treatment versus control (1:1). Control patients will be allowed to cross-over at the completion of the blinded phase. A parallel roll-in arm will enroll up to 2 patients per site in an open-label study.
Primary purpose: TREATMENT

Brief summary: The objective of the RELIEVE-HF study is to provide reasonable assurance of safety and effectiveness of the V-Wave Interatrial Shunt System by improving meaningful clinical outcomes in patients with New York Heart Association (NYHA) functional Class II, Class III, or ambulatory Class IV heart failure (HF), irrespective of left ventricular ejection fraction, who at baseline are treated with guideline-directed drug and device therapies.

Detailed description: This is a prospective, multi-center, 1:1 randomized, patient and observer blinded clinical study, with a Shunt Treatment arm and a non-implant Control arm. A total of approximately 500 patients will be randomized. Patients and all research staff managing the patients after randomization will be blinded during follow-up for a minimum of 12 months to a maximum of 24 months. Control patients will have the opportunity to receive a shunt after 24 months once unblinding occurs, if they provide consent, and continue to meet inclusion/exclusion criteria. All implanted patients will be followed for a total of 5 years from the time of the study device implantation.

Eligibility criteria: Main Inclusion Criteria:

* Both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) patients
* NYHA Class II, Class III, or ambulatory Class IV HF
* Receiving guideline directed medical and device therapy (GDMT) for heart failure
* For NYHA Class III and ambulatory Class IV, at least one prior hospitalization for heart failure within the last year or elevated BNP level of at least 300 pg/ml or NT-proBNP level of at least 1,500 pg/ml. BNP/NT-ProBNP levels corrected for BMI
* For NYHA Class II, must have both hospitalization and elevated BNP levels as above specifications

Main Exclusion Criteria:

* Systolic blood pressure \<90 or \>160 mmHg
* Presence of Intracardiac thrombus
* Pulmonary hypertension with PASP of ≥70 mm/Hg or PVR \> 4 WU
* Significant RV dysfunction - TAPSE \<12mm or RVFAC ≤25%
* Left Ventricular End-Diastolic Diameter (LVEDD) \>8cm
* Moderate to severe aortic or mitral stenosis
* Stroke or TIA or DVT within the last 6 months
* eGFR \<25 ml/min/1.73 m\^2
* Anatomical anomaly on TEE or ICE that precludes implantation of Shunt across fossa ovalis (FO) of the interatrial septum
* Inadequate vascular access for implantation of shunt, e.g. femoral venous access for transseptal catheterization and inferior vena cava (IVC) is not patent
* Hemodynamic heart rhythm, or respiratory instability at time of Final Exclusion Criteria

Primary outcomes:
measure: Safety-Percentage of Treatment patients experiencing major device-related adverse events
timeFrame: 30-days after randomization
measure: Effectiveness-Hierarchical composite of death, heart transplant or left ventricular assist device (LVAD) implantation, HF hospitalizations, worsening HF events treated as an outpatient, and change in Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Follow-up duration at endpoint analysis ranges from a minimum of 12 to a maximum of 24 months
Secondary outcomes:
measure: 6MWT changes
timeFrame: Baseline to 12 months
measure: KCCQ changes
timeFrame: Baseline to 12 months
measure: KCCQ changes
timeFrame: Baseline through study completion, maximum of five years
measure: Time to all-cause death, LVAD/Transplant, or heart failure hospitalization
timeFrame: Baseline through study completion, maximum of five years
measure: Time to all-cause death or first heart failure hospitalization
timeFrame: Baseline through study completion, maximum of five years
measure: Cumulative heart failure hospitalizations
timeFrame: Baseline through study completion, maximum of five years
measure: Time to first heart failure hospitalization
timeFrame: Baseline through study completion, maximum of five years
measure: Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ
timeFrame: Baseline through study completion, maximum of five years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Abrazo Arizona Heart Hospital
state: Arizona
city: Phoenix
country: United States
facility: Arizona Heart Rhythm Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford Hospital
state: California
city: Thousand Oaks
country: United States
facility: Los Robles Hospital & Medical Center
state: California
city: Torrance
country: United States
facility: The Lundquist Institute (Harbor-UCLA) Medical Center
state: California
city: Littleton
country: United States
facility: South Denver Cardiology
state: Colorado
city: Jacksonville
country: United States
facility: Memorial Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orange Park
country: United States
facility: First Coast Cardiovascular Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Midwest Cardiovascular Institute
state: Illinois
city: Edgewood
country: United States
facility: St Elizabeth Medical Center
state: Kentucky
city: Saint Paul
country: United States
facility: United Heart & Vascular Clinic
state: Minnesota
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Ridgewood
country: United States
facility: Valley Health System
state: New Jersey
city: New York
country: United States
facility: Weill Cornell
state: New York
city: New York
country: United States
facility: Northwell Health Lenox Hill Hospital
state: New York
city: Rochester
country: United States
facility: Rochester General Health System
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Heart & Vascular
state: North Carolina
city: Akron
country: United States
facility: Summa Health
state: Ohio
city: Cincinnati
country: United States
facility: Lindner Center for Research and Education at The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Wormleysburg
country: United States
facility: UPMC Pinnacle / Pinnacle Health Cardiovascular Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Houston
country: United States
facility: University of Texas Memorial Hermann
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital
state: Texas
city: Tyler
country: United States
facility: Christus Mother Frances Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Richmond
country: United States
facility: Chippenham Medical Center
state: Virginia
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital Sydney
state: New South Wales
city: Adelaide
country: Australia
facility: Flinders Medical Centre
city: Brisbane
country: Australia
facility: Prince Charles Hospital
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
city: Richmond
country: Australia
facility: Epworth Hospital
city: Antwerp
country: Belgium
facility: Ziekenhuis Aan De Stroom vzw (ZAS)
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Montréal
country: Canada
facility: Montréal Heart Institute
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain
city: Berlin
country: Germany
facility: Vivantes Klinikum Urban
city: Hamburg
country: Germany
facility: Marienkrankrankenhas
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Mainz
country: Germany
facility: Universitatsmedizin Mainz
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München
city: Remscheid
country: Germany
facility: SANA Remscheid
city: Rostock
country: Germany
facility: University of Rostock
city: Ashdod
country: Israel
facility: University Hospital Samson Assuta Ashdod
city: Be'er Ya'aqov
country: Israel
facility: Yitzhak Shamir Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center Tel-Hashomer
city: Rechovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tiberias
country: Israel
facility: The Baruch Padeh Medical Center, Poriya
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis Nieuwegein
state: Utrecht
city: Amsterdam
country: Netherlands
facility: Academic Medical Center, The Netherlands
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center Rotterdam
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Katowice
country: Poland
facility: Górnośląskie Centrum Medyczne, Uniwersytetu Medycznego w Katowicach
city: Warszawa
country: Poland
facility: Institute of Cardiology, Warsaw
city: Wrocław
country: Poland
facility: The 4th Military Clinical Hospital Wroclaw
city: Wrocław
country: Poland
facility: University Hospital Wroclaw
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol, Badalona Barcelona
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro-Majadahonda
city: Murcia
country: Spain
facility: University Hospital Virgen de la Arrixaca
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Bern
country: Switzerland
facility: Bern University Hospital
city: Zürich
country: Switzerland
facility: University Hospital of Zürich
Study officials:
affiliation: University Medical Center Gottingen, Germany
name: Stefan D Anker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: JoAnn Lindenfeld, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Université Laval (CRIUCPQ-ULaval)
name: Josep Rodés-Cabau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Colombia University Medical Center
name: Gregg W Stone, MD
role: PRINCIPAL_INVESTIGATOR
References: