REDUCE LAP-HF RANDOMIZED TRIAL I
Research type
Research Study
Full title
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
IRAS ID
194132
Contact name
Clare Huntington
Contact email
Sponsor organisation
Corvia Medical, Inc.
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Research Summary
Heart failure(HF) has been described as the “new” or “emerging” epidemic of the 21st century. It is a complex clinical syndrome that can result from any structural or functional cardiac or cardiovascular disorder that impairs the ability of the left ventricle to fill with or eject blood.
Corvia Medical has developed the InterAtrial Shunt Device (IASD) System II designed to reduce left atrial pressure, with a standard catheter based approach. 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 elevated left atrial pressure.
The primary objective of this randomized controlled clinical study is to evaluate the safety and potential effectiveness of the procedure of implantation of the IASD System II in patients suffering from heart failure.
The IASD® System II might help to improve the quality of life and reduce heart failure related symptoms and events in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF) with elevated left atrial pressure, whose symptoms remain despite appropriate medical management.
After qualification procedures, patients who are eligible for the study are randomized to either the treatment or control group. Patient randomization will be done automatically via IWRS (Interactive Web Response System). All patients will be sedated, and both treatment and control arm patients will require femoral venous access.
Up to 60 subjects will be enrolled to this study at up to 20 investigational sites in the U.S.; and up to 8 investigational sites outside of the US will randomize 40 patients and obtain 1 month hemodynamic follow-up.
Total study duration is 74 months. All patients, including cross-over patients will be followed for 1 year, and annually every 12 months for a total of 5 years after index procedure and implant.Summary of Results
Key Outcome Measures:
Key Safety Measure: The primary safety outcome measure was peri-procedural and 1-month major adverse cardiac, cerebrovascular, and renal events (MACCRE) defined as:
1. Cardiovascular death through 1 month post implant; 2. Embolic stroke through 1 month post implant; 3. Device and or procedure related adverse cardiac events through 1 month post implant; 4. New onset or worsening of kidney dysfunction (defined as estimated glomerular filtration rate [eGFR] decrease of > 20 mL/min) through 1-month post implant.Key Effectiveness (Mechanistic Effect) Measure: Change in supine exercise pulmonary capillary wedge pressure (PCWP) at 1 month, as assessed by an independent blinded hemodynamic core laboratory, across the four values measured at each visit (values at 20W, 40W, 60W and 80W).
Key Secondary Outcome Measures:
1. Change in exercise peak PCWP from baseline at 1 month. Exercise peak PCWP was defined as the PCWP measured at peak exercise workload.
2. Cardiovascular death through 12 months.
3. Rate of total (first plus recurrent) HF admissions/emergency clinic visits or acute care facilities for intravenous (IV) diuresis for HF through 12 months.
4. Change in quality of life (QOL) (EuroQol Five Dimensions Questionnaire [EQ-5D] and Kansas City Cardiomyopathy Questionnaire [KCCQ] score) at 12 months.
Additional Outcome Measures: Safety-Related Outcome Measures:
1. Major adverse cardiac events (MACE) through 12-months 2. All serious adverse events (SAEs) through 12-months 3. All-cause mortality, cardiovascular mortality and HF related mortality through 12-months 4. Newly acquired persistent or permanent atrial fibrillation (AF) or atrial flutter through 12-months 5. Implant embolization and clinically significant device migration through 12-months 6. Systemic embolic events through 12-months 7. Increase in right ventricle (RV) size/decrease in RV function through 12-months 8. The need for implant removal or occlusion of the implant.
Efficacy-Related Outcome Measures:
1. All-cause, and HF related hospitalizations/emergency department visits with IV treatment for HF; and number of hospitalization days, intensive care unit (ICU) days through 12 months 2. Treatment for outpatient worsening of HF 3. Days alive, and not-hospitalized through 12-months 4. Change in blinded Investigator assessed New York Heart Association (NYHA) classification between baseline and 12 months 5. Change in 6-minute walk test (6MWT) distance between baseline and 12 months 6. Assessment of shunt dimensions and flow at 12 months 7. Changes in resting and exercise pulmonary artery pressures (PAP) and cardiac index between baseline and 1 month as assessed by an independent blinded hemodynamic core laboratory
8. Change in B-type natriuretic peptide (BNP) and/or N-terminal pro B-type natriuretic peptide (NT-pro-BNP) between baseline and at 12 months. Midregional atrial natriuretic peptide (MR-ANP) was optional.
9. Changes in left atrium (LA), left ventricle (LV) dimensions, volume, and function, between baseline and 12 months assessed by an independent echocardiographic core laboratory 10. Changes in right atrium (RA), LA, LV and RV dimensions, volume, and function between baseline and 12 months assessed by a cardiac magnetic resonance imaging (MRI) core laboratory (Sub-study only) 11. Change in cardiopulmonary exercise test (CPET) parameters (including exercise time) between baseline and 12 months as assessed by an independent blinded CPET core laboratory (Sub-study only) 12. Change in diuretic medications between baseline and 12 months.Results: This 5-Year Final Report repeats the analyses of key and secondary safety and effectiveness outcome measures through 12 months and provides long-term analyses through the end of study at 5 years post-procedure. Data from Cross-Over subjects starting from the cross-over procedure are analyzed and reported separately.
All 44 randomized subjects (22 Treatment subjects and 22 Control subjects) comprise the ITT population. The Per Protocol (PP) population consists of 42 subjects: 20 Treatment subjects and 22 Control subjects. Two subjects randomized to the Treatment arm were excluded from the PP population for not undergoing a successful implant procedure.
REC name
West of Scotland REC 4
REC reference
16/WS/0025
Date of REC Opinion
23 Mar 2016
REC opinion
Further Information Favourable Opinion