NIPH Clinical Trials Search

JRCT ID: jRCT1080224934

Registered date:31/10/2019


Basic Information

Recruitment status recruiting
Health condition(s) or Problem(s) studiedHeart failure with elevated left atrial pressure
Date of first enrollment05/12/2019
Target sample size30
Countries of recruitmentJapan,USA,Canada,Australia,Germany,France,Italy,Croatia,Belgium,Netherlands,Poland,Spain,United Kingdom,Austria
Study typeInterventional
Intervention(s)investigational material(s) Generic name etc : To Be Determined INN of investigational material : - Therapeutic category code : - Dosage and Administration for Investigational material : The permanent implant pre-loaded onto a delivery system is placed across the interatrial septum using a percutaneous trans-catheter approach. control material(s) Generic name etc : - INN of investigational material : - Therapeutic category code : - Dosage and Administration for Investigational material : Non-implant, Sham Control


Primary OutcomeThe 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, and time-to-first HF event; and (c) change in baseline KCCQ total summary score at 12 months.
Secondary Outcome< Major Secondary endpoints > 1. Composite safety endpoint defined as follows: a. Cardiovascular mortality through 12 months b. Non-fatal, ischemic stroke through 12 months c. New onset or worsening of kidney dysfunction (defined as eGFR decrease of > 20 ml/min/1.73 m2) through 12 months d. Major adverse cardiac events through 12-months defined as i. Cardiac death ii. Myocardial infarction iii. Cardiac tamponade iv. Emergency cardiac surgery e. Thrombo-embolic complications (TIA, systemic embolization) through 12 months f. Newly acquired persistent or permanent AF or atrial flutter through 12-months g. >= 30% increase in RV size/decrease in TAPSE through 12-months 2. 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, 3. Change in NYHA functional Class assessed by a blinded physician between baseline and 12 months, 4. Change in KCCQ score between baseline and 12 months, categorized as =<0, >0 - 5, >5 - 10, >10 - 15, >15 - 20, >20 - 25, >25. < Secondary Outcome Measures > 1. All serious adverse events (SAEs) through 12-months 2. All-cause mortality through 12-months 3. Heart failure related mortality through 12-months 4. Implant embolization and clinically significant device migration through 12-months 5. The need for implant removal or occlusion of the implant through 12-months. Efficacy related outcome measures: 6. Rate of total (first plus recurrent) per patient year of 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 as adjudicated by CEC. 7. Number of heart failure related hospitalization days and number of all ICU days through last follow-up, analyzed, as adjudicated by CEC. 8. Treatment for outpatient worsening of heart failure through last follow-up, as adjudicated by CEC. 9. Days alive, and days not-hospitalized through last follow-up 10. Change in diuretic medications (number of medications and dosages) between baseline and 6 & 12 months.

Key inclusion & exclusion criteria

Age minimum>= 40age old
Age maximumNot applicable
Include criteriaCandidates for the study must meet ALL of the following inclusion criteria: 1. Chronic symptomatic heart failure (HF) documented by the following: a. Symptoms of HF requiring current treatment with diuretics for >= 30 days AND b. New York Heart Association (NYHA) class II if a prior 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 visit; or signs (any rales post cough, chest x-ray demonstrating pulmonary congestion,) within past 12 months; AND c. >= 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV); or the need for 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. 2. Ongoing stable GDMT HF management and management of potential comorbidities according to the 2022 ACC/AHA Guidelines for the Management of Heart Failure, with no significant changes (>100% increase or 50% decrease), excluding diuretic dose changes, for a minimum of 4 weeks prior to enrollment which is expected to be maintained for 6 months. Stable management includes a minimum period of 4 weeks post hospitalization for any cause, including treatment with IV diuretics. 3. Age >= 40 years old 4. Site determined echocardiographic LV ejection fraction >= 40% within the past 6 months, without documented ejection fraction <30% in the 5 years prior to study entry. 5. Site determined elevated PCWP with a gradient compared to right atrial pressure (RAP) documented by: a. End-expiratory PCWP during supine ergometer exercise >= 25mm Hg, and greater than RAP by >= 5 mm Hg. 6. Site determined hemodynamic evidence of peak exercise PVR < 1.75 Wood units 7. Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following: a. LA diameter > 4 cm; or b. Diastolic LA volume > 50 or LA volume index > 28 ml/m2 or c. Lateral e < 10 cm/s; or d. Septal e < 8 cm/s; or e. Lateral E/e > 10; or f. Septal E/e > 15 8. Subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the IRB or EC 9. Subject is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams 10. Trans-septal catheterization and femoral vein access to the right atrium is determined to be feasible by site interventional cardiology investigator.
Exclude criteriaCandidates for this study will be excluded if ANY of the following conditions are present: 1. 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; or a planned cardiac interventions in the 3 months following enrollment 2. Any cardiac rhythm device 3. Advanced heart failure defined as one or more of the below: a. ACC/AHA/ESC Stage D heart failure, Non-ambulatory NYHA Class IV HF; b. Cardiac index < 2.0 L/min/m2 c. Inotropic infusion (continuous or intermittent) for EF < 40% within the past 6 months d. Patient is on the cardiac transplant waiting list 4. Inability to perform 6 minute walk test (distance < 50 m), OR 6 minute walk test > 600m 5. The patient has verified that the ability to walk 6 minutes is limited primarily by joint, foot, leg, hip or back pain; unsteadiness or dizziness or lifestyle (and not by shortness of breath and/or fatigue and/or chest pain). 6. This space was intentionally left blank 7. Known clinically significant un-revascularized coronary artery disease, defined as: epicardial coronary artery stenosis with angina or other evidence of ongoing active coronary ischemia. 8. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months 9. Known clinically significant untreated carotid artery stenosis likely to require intervention. 10. Presence of hemodynamically significant valve disease assessed by the site cardiologist and defined as: a. Mitral valve disease defined as grade >= 3+ MR or > mild MS; OR b. Tricuspid valve regurgitation defined as grade >= 2+ TR; OR c. Aortic valve disease defined as >= 2+ AR or > moderate AS 11. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or other infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis) 12. Subject is contraindicated to receive either dual antiplatelet therapy, or an oral anticoagulant; or has a documented coagulopathy 13. Atrial fibrillation with resting HR > 100 BPM 14. Resting arterial oxygen saturation < 95% on room air 15. Significant hepatic impairment defined as 3X upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase 16. Right ventricular dysfunction, assessed by the site cardiologist and defined as a. More than mild RV dysfunction as estimated by TTE; OR b. TAPSE < 1.4 cm; OR c. RV size >= LV size as estimated by TTE; OR d. Ultrasound or clinical evidence of congestive hepatopathy; OR e. Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%; 17. Resting RAP > 14 mmHg 18. Chronic pulmonary disease requiring continuous home oxygen, OR significant chronic pulmonary disease defined as FEV1 <1L. 19. Hemoglobin <10 g/dl 20. Currently participating in an investigational drug or device study that would interfere with the conduct or results of this study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational 21. Life expectancy less than 12 months for known non-cardiovascular reasons 22. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation 23. Known or suspected allergy to nickel 24. Women of child-bearing potential 25. Currently requiring dialysis; or estimated-GFR <25ml/min/1.73 m2 by Japan Society of Nephrology equation 26. Systolic blood pressure >170 mm Hg at screening 27. Subjects with existing or surgically closed (with a patch) atrial septal defects, subjects with a percutaneously closed ASD or PFO. Subjects with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are not excluded. 28. Subjects on significant immunosuppressive treatment or on systemic steroid treatment (> 10 mg prednisone/day). 29. Severe obstructive sleep apnea not treated with CPAP or other measures 30. Severe depression and/or anxiety 31. In the opinion of the investigator, the subject is not an appropriate candidate for the study 32. BMI > 40.

Related Information


Public contact
Name Masashi Hirata
Address Hamamatsucho Bldg., 1-1-1 Shibaura, Minato-ku, Tokyo 105-0023, JAPAN
Telephone +81-3-6779-8000
Affiliation CMIC Co., Ltd.
Scientific contact
Name Kate Stohlman
Address One Highwood Drive, Suite 300, Tewksbury, MA 01876 USA
Telephone 1-978-654-6110
Affiliation Corvia Medical, Inc.