REDUCE LAP-HF RANDOMIZED TRIAL I

Study Overview
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Brief Summary
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A study to evaluate the Corvia Medical, Inc. IASD® System II to REDUCE Elevated Left Atrial Pressure in Patients with Heart Failure.

Detailed Description
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The primary objective of this randomized controlled clinical study is to evaluate the peri-procedural safety and potential effectiveness (mechanistic effect) of implanting the IASD System II in heart failure patients with an LV ejection fraction >40%, elevated left sided filling pressures, and who remain symptomatic despite optimal Guideline Directed Medical Therapy (GDMT). Clinical outcomes will also be evaluated.

Official Title
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REDUCE LAP-HF RANDOMIZED TRIAL I: A Study to Evaluate the Corvia Medical, Inc. IASD® System II to REDUCE Elevated Left Atrial Pressure in Patients With Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Inter-Atrial Shunt Device
* Other: Intracardiac Echo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Chronic symptomatic Heart Failure Ongoing stable GDMT HF management and management of potential comorbidities Age ≥ 40 years old LV ejection fraction ≥ 40% within the past 3 months, without previously documented ejection fraction <30%. Elevated left atrial pressure with a gradient compared to right atrial pressure (RAP) documented by end-expiratory PCWP during supine ergometer exercise ≥ 25mm Hg, and greater than RAP by ≥ 5 mm Hg Key Exclusion Criteria: MI and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization Cardiac Resynchronization Therapy initiated within the past 6 months Severe heart failure 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 Known clinically significant untreated carotid artery stenosis Currently requiring dialysis; or estimated-GFR <25ml/min/1.73 m2 by CKD-Epi equation

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Inter-Atrial Shunt Device<br>Once all study criteria have been met, if randomized to this arm, patients will receive the IASD implant. | Device: Inter-Atrial Shunt Device<br>* An implantable device placed in the interatrial septum<br>* Other names: IASD;|
| Placebo Comparator: Control<br>Once all study criteria have been met, if randomized to this arm, patients will not receive the implant. They will undergo an intracardiac echo only, with the option to crossover at 1 year. | Other: Intracardiac Echo<br>* Patients randomized to the control arm will undergo intra cardiac echocardiography, with examination of the atrial septum and left atrial appendage.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peri-procedural, and 1 month Major Adverse Cardiac, Cerebrovascular, and Renal Events (MACCRE) | The primary safety outcome measure is the incidence of one or more of the following major adverse cardiac, cerebrovascular embolic, or renal events (MACCRE) defined as: Cardiovascular death through 1-month post implant; Embolic stroke through 1-months post implant; Device and or procedure related adverse cardiac events through 1-month post implant; New onset or worsening of kidney dysfunction (defined as eGFR decrease of > 20 ml/min) through 1-month post implant | 1 Month Post Implant | 
| Change in supine exercise pulmonary capillary wedge pressure (PCWP) | Change in supine exercise pulmonary capillary wedge pressure (PCWP), as assessed by an independent blinded hemodynamic core laboratory, across the four values measured at each visit (values at 20W, 40W, 60W and 80W). | 1 Month Post Implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in exercise PEAK pulmonary capillary wedge pressure (PCWP) from baseline |  | 1 Month | 
| Cardiovascular death |  | 12 Months | 
| Rate of total (first plus recurrent) HF admissions/emergency clinic visits or acute care facilities for IV diuresis for HF |  | 12 Months | 
| Change in Quality Of Life Questionnaire (EQ-5D) |  | 12 Months | 
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ score) |  | 12 Months |