Reducing Lung CongestIon Symptoms in Advanced Heart Failure (RELIEVE-HF)

• ClinicalTrials.gov Identifier: NCT03499236
• Recruitment Status: Active, not recruiting
• First Posted: April 17, 2018
• Last Update Posted: February 27, 2023
• Sponsor: V-Wave Ltd
• Information provided by (Responsible Party): V-Wave Ltd

Tracking Information

• First Submitted Date: March 29, 2018
• First Posted Date: April 17, 2018
• Last Update Posted Date: February 27, 2023
• Actual Study Start Date: September 19, 2018
• Estimated Primary Completion Date: October 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2021)

• Safety-Percentage of Treatment patients experiencing major device-related adverse events [ Time Frame: 30-days after randomization ]
  Percentage of Treatment group patients experiencing any device-related Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 30-days after randomization, compared to a pre-specified Performance Goal
• 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) [ Time Frame: Follow-up duration at endpoint analysis ranges from a minimum of 12 to a maximum of 24 months ]
  Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method

Original Primary Outcome Measures (submitted: April 13, 2018)

• Safety-Percentage of Treatment patients experiencing major device-related adverse events [ Time Frame: 30-days after randomization ]
  Percentage of Treatment group patients experiencing any device-related Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 30-days after randomization, compared to a pre-specified Performance Goal
• Effectiveness-Hierarchical composite of death, heart transplant or left ventricular assist device (LVAD) implantation, HF hospitalizations, and change in six minute walk test (6MWT). [ Time Frame: Follow-up duration at endpoint analysis ranges from a minimum of 12 to a maximum of 24 months ]
  Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method

Current Secondary Outcome Measures (submitted: December 1, 2021)

• 6MWT changes [ Time Frame: Baseline to 12 months ]
  6MWT changes
• KCCQ changes [ Time Frame: Baseline to 12 months ]
  KCCQ changes
• KCCQ changes [ Time Frame: Baseline through study completion, maximum of five years ]
  KCCQ changes
• Time to all-cause death, LVAD/Transplant, or heart failure hospitalization [ Time Frame: Baseline through study completion, maximum of five years ]
  Time to all-cause death, LVAD/Transplant, or heart failure hospitalization
• Time to all-cause death or first heart failure hospitalization [ Time Frame: Baseline through study completion, maximum of five years ]
  Time to all-cause death or first heart failure hospitalization
• Cumulative heart failure hospitalizations [ Time Frame: Baseline through study completion, maximum of five years ]
  Cumulative heart failure hospitalizations
• Time to first heart failure hospitalization [ Time Frame: Baseline through study completion, maximum of five years ]
  Time to first heart failure hospitalization
• Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ [ Time Frame: Baseline through study completion, maximum of five years ]
  Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ

Original Secondary Outcome Measures (submitted: April 13, 2018)

• Change in 6MWT [ Time Frame: Baseline to 12 months ]
  Comparison between Treatment and Control groups of change in 6MWT
• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: Baseline to 12 months ]
  Comparison between Treatment and Control groups of change in KCCQ

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

In the randomized cohort, participants, the clinical team, and research staff managing the patient after randomization will be blinded to study assignment.

Primary Purpose: Treatment

• Condition: Heart Failure

Intervention

• Device: V-Wave Interatrial Shunt
  The V-Wave Interatrial Shunt System, includes a permanent implant placed during a minimally invasive cardiac catheterization procedure using its dedicated Delivery Catheter. The device is implanted through the fossa ovalis and straddles the interatrial septum.
• Other: Control
  Right heart catheterization, invasive echocardiography.

Study Arms

• Experimental: Treatment
  Treatment arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by transseptal catheterization and V-Wave Shunt implantation
  Intervention: Device: V-Wave Interatrial Shunt
• Control
  Control arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility, but will not have transseptal catheterization or shunt implantation.
  Intervention: Other: Control
• Experimental: Roll in
  Roll in arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by transseptal catheterization and V-Wave Shunt implantation
  Intervention: Device: V-Wave Interatrial Shunt

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 26, 2022): 605
• Original Estimated Enrollment (submitted: April 13, 2018): 500
• Estimated Study Completion Date: October 31, 2027
• Estimated Primary Completion Date: October 15, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Germany, Israel, Netherlands, New Zealand, Poland, Spain, Switzerland, United States
• Removed Location Countries: Georgia

Administrative Information

• NCT Number: NCT03499236
• Other Study ID Numbers: CL7018
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: V-Wave Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: V-Wave Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stefan D Anker, MD, PhD; University Medical Center Gottingen, Germany
• Principal Investigator: JoAnn Lindenfeld, MD; Vanderbilt University
• Principal Investigator: Josep Rodés-Cabau, MD; Université Laval (CRIUCPQ-ULaval)
• Principal Investigator: Gregg W Stone, MD; Colombia University Medical Center

• PRS Account: V-Wave Ltd
• Verification Date: October 2022