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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05425459




Registration number
NCT05425459
Ethics application status
Date submitted
13/06/2022
Date registered
21/06/2022
Date last updated
1/07/2024

Titles & IDs
Public title
RESPONDER-HF Trial
Scientific title
Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction (EF) Heart Failure (Protocol #2201)
Secondary ID [1] 0 0
2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Heart Failure, Diastolic 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Corvia Atrial Shunt System / IASD System II
Other interventions - Intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE)

Experimental: Treatment - Participants randomized to the treatment arm will undergo a fluoroscopic and intra-cardiac echocardiography (ICE), or transesophageal echocardiography (TEE) guided trans-septal puncture and InterAtrial Shunt Device (IASD) System II implant procedure.

Sham comparator: Control - Participants randomized to the control arm will undergo fluoroscopy and intracardiac echocardiography from the femoral vein or transesophageal echocardiography, for examination of the atrial septum and left atrial appendage.


Treatment: Devices: Corvia Atrial Shunt System / IASD System II
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 interventions: 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.
Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite Primary Endpoint
Timepoint [1] 0 0
Up to 12 months
Secondary outcome [1] 0 0
The incidence of cardiovascular mortality
Timepoint [1] 0 0
Up to 12 months
Secondary outcome [2] 0 0
The rate of time-to-cardiovascular mortality
Timepoint [2] 0 0
Up to 12 months
Secondary outcome [3] 0 0
The rate of major adverse cardiac periprocedural events
Timepoint [3] 0 0
Through 30 days
Secondary outcome [4] 0 0
The incidence of non-fatal, ischemic stroke
Timepoint [4] 0 0
Through 12 months
Secondary outcome [5] 0 0
The rate of new onset or worsening of kidney dysfunction
Timepoint [5] 0 0
Through 12 months
Secondary outcome [6] 0 0
The incidence of thrombo-embolic complications including transient ischaemic attack (TIA) and systemic embolization)
Timepoint [6] 0 0
Through 12 months
Secondary outcome [7] 0 0
The incidence of newly acquired persistent or permanent atrial fibrillation (AF) or atrial flutter
Timepoint [7] 0 0
Through 12 months
Secondary outcome [8] 0 0
The incidence of participants with a =30% decrease in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Timepoint [8] 0 0
Through 12 months
Secondary outcome [9] 0 0
The rate of heart failure (HF) admissions
Timepoint [9] 0 0
Through 24 months
Secondary outcome [10] 0 0
The change in New York Heart Association (NYHA) Class
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
The change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score
Timepoint [11] 0 0
12 months

Eligibility
Key inclusion criteria
1. Chronic symptomatic heart failure (HF) documented by the following:

1. Symptoms of HF requiring current treatment with diuretics if tolerated for = 30 days AND
2. New York Heart Association (NYHA) class II; OR NYHA class III, or ambulatory NYHA class IV symptoms; AND
3. = 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV) diuretics; or intensification of oral diuresis within the 12 months prior to study entry; OR an NT-proB-type Natriuretic Peptide (NT-pro BNP) value > 150 pg/ml in normal sinus rhythm, > 450 pg/ml in atrial fibrillation, or a brain natriuretic peptide (BNP) value > 50 pg/ml in normal sinus rhythm, > 150 pg/ml in atrial fibrillation within the past 6 months
2. Ongoing stable guideline-directed medical therapy (GDMT) HF management and management of comorbidities according to the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Heart Failure. Stable management includes a minimum period of 4 weeks post-hospitalization for any cause, including treatment with IV diuretics
3. Site determined echocardiographic LV ejection fraction = 40% within the past 6 months, without documented ejection fraction < 30% in the 5 years prior.
4. Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following:

1. Left Atrial (LA) diameter > 4 cm; or
2. Diastolic LA volume > 50 or LA volume index > 28 ml/m2 or
3. Lateral e' < 10 cm/s; or
4. e' < 8 cm/s; or
5. Site determined elevated pulmonary capillary wedge pressure (PCWP) with a gradient compared to right atrial pressure (RAP) documented by end-expiratory PCWP during supine ergometer exercise = 25 millimeters of mercury (mm Hg), and greater than RAP by = 5 mm Hg.
6. Resting RAP = 14 mmHg
7. Site determined hemodynamic evidence of peak exercise pulmonary vascular resistance (PVR) < 1.75 Wood units
8. Age = 40 years old
9. Participant has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the Institutional Review Board (IRB) or Ethics Committee (EC)
10. Participant is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams
11. Transseptal catheterization and femoral vein access to the right atrium is determined to be feasible by site interventional cardiology investigator.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Advanced heart failure defined as one or more of the below:

1. ACC/AHA/European Society of Cardiology (ESC) Stage D heart failure, non-ambulatory NYHA Class IV HF
2. Cardiac index < 2.0 L/min/m2
3. Inotropic infusion (continuous or intermittent) for EF < 40% within the past 6 months
4. Patient is on the cardiac transplant waiting list.
2. Inability to perform 6-minute walk test (distance < 50 meters), OR 6-minute walk test > 600m
3. 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)
4. Right ventricular dysfunction, assessed by the site cardiologist and defined as one or more of the following:

1. More than mild right ventricular (RV) dysfunction as estimated by transthoracic echocardiogram (TTE); OR
2. TAPSE < 1.4 cm; OR
3. Right ventricular (RV) size = left ventricular (LV) size as estimated by TTE; OR
4. Ultrasound or clinical evidence of congestive hepatopathy; OR
5. Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%.
5. Any implanted cardiac rhythm device
6. Structural heart repair aortic valve replacement (AVR) or mitral valve replacement (MVR) (surgical or percutaneous) within the past 12 months; planned valve intervention in the next 3 months, or presence of hemodynamically significant valve disease as assessed by the site cardiologist and defined as:

1. Mitral valve disease grade = 3+ mitral regurgitation (MR) or > mild Mitral Stenosis (MS); OR
2. Tricuspid valve (TR) regurgitation grade = 2+ TR; OR
3. Aortic valve disease = 2+ aortic regurgitation (AR) or > moderate aortic stenosis (AS)
7. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation
8. Participants with existing or surgically closed (with a patch) atrial septal defects. Participants with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are not excluded
9. Myocardial Infarction (MI) and/or percutaneous cardiac intervention within past 3 months; Coronary Artery Bypass Graft (CABG) surgery in past 3 months or any planned cardiac interventions in the 3 months following enrollment.
10. Known clinically significant un-revascularized coronary artery disease, defined as: coronary artery stenosis with angina or other evidence of ongoing active coronary ischemia
11. Known clinically significant untreated carotid artery stenosis likely to require intervention
12. Atrial fibrillation with resting heart rate (HR) > 100 beats-per-minute (BPM)
13. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis)
14. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
15. Participant is contraindicated to receive either dual antiplatelet therapy, or an oral anticoagulant; or has a documented coagulopathy
16. Anemia with Hemoglobin < 10 g/dl
17. Chronic pulmonary disease requiring continuous home oxygen, OR significant chronic pulmonary disease defined as forced expiratory volume (FEV)1 <1Liter
18. Resting arterial oxygen saturation < 95% on room air, <93% when residing at high altitude
19. Currently requiring dialysis; or estimated glomerular filtration rate eGFR < 25ml/min/1.73 m2 by chronic kidney disease (CKD) CKD-Epi equation
20. Systolic blood pressure > 170 mm Hg at screening
21. Significant hepatic impairment defined as 3 times upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
22. Participants on significant immunosuppressive treatment or on systemic steroid treatment
23. Life expectancy less than 12 months for known non-cardiovascular reasons
24. Known hypersensitivity to nickel or titanium
25. Women of childbearing potential
26. Severe obstructive sleep apnea not treated with continuous positive airway pressure (CPAP) or other measures
27. Body Mass Index (BMI) > 45; BMI 40 - 45 is also excluded unless in the opinion of the investigator, vascular access can be obtained safely
28. Severe depression and/or anxiety
29. 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
30. In the opinion of the investigator, the Participant is not an appropriate candidate for the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2031
Actual
Sample size
Target
750
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St. Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [3] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
4032 - Chermside
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Delaware
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
New Hampshire
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
West Virginia
Country [23] 0 0
Austria
State/province [23] 0 0
Graz
Country [24] 0 0
Belgium
State/province [24] 0 0
Aalst
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Germany
State/province [27] 0 0
Bad Krozingen
Country [28] 0 0
Germany
State/province [28] 0 0
Bad Nauheim
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Cologne
Country [31] 0 0
Germany
State/province [31] 0 0
Dresden
Country [32] 0 0
Germany
State/province [32] 0 0
Duesseldorf
Country [33] 0 0
Germany
State/province [33] 0 0
Freiburg
Country [34] 0 0
Germany
State/province [34] 0 0
Göttingen
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
Country [36] 0 0
Germany
State/province [36] 0 0
Leipzig
Country [37] 0 0
Germany
State/province [37] 0 0
Luebeck
Country [38] 0 0
Germany
State/province [38] 0 0
Münster
Country [39] 0 0
Germany
State/province [39] 0 0
Schwerin
Country [40] 0 0
Germany
State/province [40] 0 0
Ulm
Country [41] 0 0
Germany
State/province [41] 0 0
Würzburg
Country [42] 0 0
Netherlands
State/province [42] 0 0
Groningen
Country [43] 0 0
Netherlands
State/province [43] 0 0
Maastricht

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Corvia Medical
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Multicenter, Prospective, Randomized, Sham Controlled, Double Blinded Clinical Trial, with; 1:1 randomization
Trial website
https://clinicaltrials.gov/study/NCT05425459
Trial related presentations / publications
Borlaug BA, Blair J, Bergmann MW, Bugger H, Burkhoff D, Bruch L, Celermajer DS, Claggett B, Cleland JGF, Cutlip DE, Dauber I, Eicher JC, Gao Q, Gorter TM, Gustafsson F, Hayward C, van der Heyden J, Hasenfuss G, Hummel SL, Kaye DM, Komtebedde J, Massaro JM, Mazurek JA, McKenzie S, Mehta SR, Petrie MC, Post MC, Nair A, Rieth A, Silvestry FE, Solomon SD, Trochu JN, Van Veldhuisen DJ, Westenfeld R, Leon MB, Shah SJ; REDUCE LAP-HF-II Investigators. Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure. Circulation. 2022 May 24;145(21):1592-1604. doi: 10.1161/CIRCULATIONAHA.122.059486. Epub 2022 Mar 31. Erratum In: Circulation. 2022 Jul 26;146(4):e12. doi: 10.1161/CIR.0000000000001086.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Sanjiv Shah, MD
Address 0 0
Northwestern Memorial Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jan Komtebedde, DVM
Address 0 0
Country 0 0
Phone 0 0
978-654-6113
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05425459