REDUCE LAP-HF TRIAL II

• ClinicalTrials.gov Identifier: NCT03088033
• Recruitment Status: Active, not recruiting
• First Posted: March 23, 2017
• Last Update Posted: February 22, 2023
• Sponsor: Corvia Medical
• Information provided by (Responsible Party): Corvia Medical

Tracking Information

• First Submitted Date: March 14, 2017
• First Posted Date: March 23, 2017
• Last Update Posted Date: February 22, 2023
• Actual Study Start Date: June 1, 2017
• Actual Primary Completion Date: July 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2021)

Composite Primary Endpoint [ Time Frame: Up to 24 months ]

The primary endpoint is the composite of (a) incidence of and time-to-cardiovascular mortality or first non-fatal, ischemic stroke through 12 months; (b) total rate (first plus recurrent) per patient year of heart failure (HF) events, defined as hospital admissions, acute healthcare facility visits or urgent unscheduled outpatient visits for IV diuresis or intensification of oral diuretics for HF up to 24 months, analyzed when the last randomized subject completes 12 months follow-up, and time-to-first HF event; and (c) change in baseline KCCQ total summary score at 12 months.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: September 13, 2021)

• Composite safety endpoint defined as follows: [ Time Frame: 12 months ]
  1. Cardiovascular mortality
  2. Non-fatal, ischemic stroke
  3. New onset or worsening of kidney dysfunction (defined as eGFR decrease of > 20 ml/min)
  4. Major adverse cardiac events through 12-months defined as: i. Cardiac death; ii. Myocardial infarction; iii. Cardiac tamponade; iv. Emergency cardiac surgery
  5. Thrombo-embolic complications (TIA, systemic embolization)
  6. Newly acquired persistent or permanent AF or atrial flutter through
  7. ≥30% increase in RV size/decrease in TAPSE
• Rate of heart failure admissions [ Time Frame: Up to 24 months ]
  Total rate (first plus recurrent) per patient year of heart failure (HF) events, defined as hospital admissions, acute healthcare facility visits, or urgent unscheduled outpatient visits for IV diuresis or intensification of oral diuretics for HF up to 24 months, analyzed when the last randomized subject completes 12-month follow-up
• Change in NYHA Class [ Time Frame: 12 months ]
  Change in NYHA functional Class assessed by a blinded physician between baseline and 12 months
• Change in Kansas City Cardiomyopathy Questionnaire [ Time Frame: 12 months ]
  Change in KCCQ score between baseline and 12 months, categorized as ≤0, >0 - 5, >5 - 10, >10 - 15, >15 - 20, >20 - 25, >25.

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

Descriptive Information

• Brief Title: REDUCE LAP-HF TRIAL II
• Official Title: A Study to Evaluate the Corvia Medical, Inc. IASD® System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure
• Brief Summary: Multicenter, Prospective, Randomized Controlled, Blinded Trial, with a Non-implant Control group; 1:1 randomization.

Detailed Description

Following supine bicycle exercise testing to assess eligibility, the eligible patients are randomized to the treatment or control group.

All patients will be sedated, and both treatment and control arm patients will undergo placement of a femoral venous access sheath after randomization.

Patients randomized to the treatment arm will undergo a fluoroscopically and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and IASD System II implant procedure. Patients randomized to the control arm will undergo ICE from the femoral vein or TEE for examination of the atrial septum and left atrium.

Patients will be evaluated at pre-specified time intervals and followed for 5 years.

All patients will be unblinded after the 24 month follow up visit.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Device: IASD System II implant
  The primary component of the system is an implant placed in the atrial septum designed to allow left to right flow between the left atrium and right atrium to reduce the elevated left atrial pressure.
• Other: intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)
  intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) for examination of the atrial septum and left atrium.

Study Arms

• Experimental: Treatment
  Patients randomized to the treatment arm will undergo a fluoroscopically and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and IASD System II implant procedure.
  Intervention: Device: IASD System II implant
• Sham Comparator: Control
  Patients randomized to the control arm will undergo ICE from the femoral vein or TEE for examination of the atrial septum and left atrium.
  Intervention: Other: intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)

• Publications *: Shah SJ, Borlaug BA, Chung ES, Cutlip DE, Debonnaire P, Fail PS, Gao Q, Hasenfuss G, Kahwash R, Kaye DM, Litwin SE, Lurz P, Massaro JM, Mohan RC, Ricciardi MJ, Solomon SD, Sverdlov AL, Swarup V, van Veldhuisen DJ, Winkler S, Leon MB; REDUCE LAP-HF II investigators. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet. 2022 Mar 19;399(10330):1130-1140. doi: 10.1016/S0140-6736(22)00016-2. Epub 2022 Feb 1.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 10, 2018): 608
• Original Enrollment: Not Provided
• Estimated Study Completion Date: September 2026
• Actual Primary Completion Date: July 29, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

SELECT INCLUSION CRITERIA

• Chronic symptomatic Heart Failure (HF) documented by one or more of the following:

  • Symptoms of HF requiring current treatment with diuretics for ≥ 30 days AND
  • NYHA class II with a history of > NYHA class II; OR NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening; or signs (any rales post cough, chest x-ray demonstrating pulmonary congestion,) within past 12 months; AND
  • ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV), or intensification of oral diuresis for HF in a healthcare facility within the 12 months prior to study entry; OR an NT-pro BNP value > 150 pg./ml in normal sinus rhythm, > 450 pg./ml in atrial fibrillation, or a BNP value > 50 pg./ml in normal sinus rhythm, > 150 pg./ml in atrial fibrillation within the past 6 months.
• Ongoing stable GDMT HF management and management of potential comorbidities according to the 2013 ACCF/AHA Guidelines for the management of Heart Failure (with no significant changes [>100% increase or 50% decrease], excluding diuretic dose change for a minimum of 4 weeks prior to screening) that is expected to be maintained without change for 6 months
• Age ≥ 40 years old, LV ejection fraction (EF) ≥ 40% within the past 3 months, without previously documented EF <30% (within the past 3 years)
• Elevated PCWP with a gradient compared to right atrial pressure (RAP), documented by end-expiratory PCWP during supine ergometer exercise ≥ 25mmHg, and greater than RAP by ≥ 5 mmHg

SELECT EXCLUSION CRITERIA

• MI and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization; AVR (surgical AVR or TAVR) within the past 12 months.
• Cardiac Resynchronization Therapy initiated within the past 6 months

• Advanced heart failure defined as one or more of the below:

  • ACC/AHA/ESC Stage D heart failure, non-ambulatory NYHA Class IV HF;
  • Cardiac index < 2.0 L/min/m2
  • Inotropic infusion (continuous or intermittent) for EF< 40% within the past 6 months
  • Patient is on the cardiac transplant waiting list
• Inability to perform 6 minute walk test (distance < 50 m), OR 6 minute walk test > 600m
• History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months

• Presence of significant valve disease defined by the site cardiologist as:

  • Mitral valve regurgitation defined as grade ≥ 3+ MR
  • Tricuspid valve regurgitation defined as grade ≥ 2+ TR
  • Aortic valve disease defined as ≥ 2+ AR or > moderate AS
• Known clinically significant untreated carotid artery stenosis likely to require intervention
• Currently requiring dialysis; or estimated-GFR <25ml/min/1.73 m2 by CKD-Epi equation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Croatia, Denmark, France, Germany, Italy, Japan, Netherlands, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03088033
• Other Study ID Numbers: 1601
• 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: No

• Current Responsible Party: Corvia Medical
• Original Responsible Party: [Redacted]
• Current Study Sponsor: Corvia Medical
• Original Study Sponsor: [Redacted]
• Collaborators: Not Provided

Investigators

• Principal Investigator: Sanjiv Shah, MD; Northwestern Memorial Hospital
• Principal Investigator: Marty Leon, MD; Columbia University

• PRS Account: Corvia Medical
• Verification Date: February 2023