Clinical trial NCT01913613: REDUCE LAP-HF TRIAL
Official title: REDUCE LAP-HF TRIAL: A Study to Evaluate the DC Devices, Inc. IASD™ System II to REDUCE Elevated Left Atrial Pressure in Patients With Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Lead sponsor: Corvia Medical
Sponsor class: INDUSTRY
First posted: 2013-08-01
Enrollment: 64
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this clinical study is to evaluate the safety and performance of the IASD System II in the treatment of heart failure patients with elevated left atrial pressure, who remain symptomatic despite appropriate medical management.


Eligibility criteria: Key Inclusion Criteria:

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

   1. New York Heart Association (NYHA) Class II/III/ambulatory 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;
   2. One hospital admission for which HF was a major component of the hospitalization within the 12 months prior to study entry (transient heart failure in the context of myocardial infarction does not qualify);
   3. On-going management with recommended heart failure medications and comorbidities for several months according to the guidelines (2012 ESC Guidelines for diagnosis and Treatment of Acute and Chronic Heart Failure).
2. Age ≥ 40 years old
3. Left ventricular ejection fraction (obtained by echocardiography) ≥ 40%
4. Elevated left ventricular filling pressures with a gradient compared to CVP documented by :

   1. PCWP or LVEDP at rest ≥ 15 mmHg, and greater than CVP, OR
   2. PCWP during supine bike exercise ≥ 25mm Hg, and CVP \< 20 mm Hg

Key Exclusion Criteria:

3. Severe heart failure defined as:

1. ACC/AHA/ESC Stage D heart failure, Non-ambulatory NYHA Class IV HF;
2. Fick Cardiac Index \< 2.0 L/min/m2
3. Requiring inotropic infusion (continuous or intermittent) within the past 6 months
4. Patient is on the cardiac transplant waiting list 4. Inability to perform 6 Minute Walk Test 5. Known significant coronary artery disease (stenosis \>70%) 6. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months 7. Known severe carotid artery stenosis (\> 70%) 8. Presence of significant valve disease defined by echocardiography as: a) Mitral valve regurgitation defined as grade \>2+ MR b) Tricuspid valve regurgitation defined as grade ≥ 2+ TR; c) Aortic valve disease defined as ≥ 2+ AR or moderate AS

Primary outcomes:
measure: MACCE
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
city: Melbourne
country: Australia
facility: David Kaye
city: Sydney
country: Australia
facility: St. Vincent Hospital
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus Univesitäts Kliniken
city: Aalst
country: Belgium
facility: OLVZ Aalst
city: Prague
country: Czechia
facility: Homolka Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Lille
country: France
facility: CHRU de Lille
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital La Pitié Salpétrière
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Dusseldorf
country: Germany
facility: Universitatklinikum Duseldorf
city: Gottingen
country: Germany
facility: Georg-August-Universitat
city: Hamburg
country: Germany
facility: Asklepios Klinik St George
city: Hamburg
country: Germany
facility: Cardiologicum CRC
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Kiel
country: Germany
facility: Universtitaät Kliniku Schlewig Holstein
city: Munich
country: Germany
facility: Klinikum der Universität Munchen
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Wroclaw
country: Poland
facility: Fourth Military Hospital
city: Glasgow
country: United Kingdom
facility: Golden Jubilee Hospital
city: Harefield
country: United Kingdom
facility: Royal Brompton/Harefield Trust
city: London
country: United Kingdom
facility: King's College
Study officials:
affiliation: Corvia Medical
name: Jan Komtebedde, DVM
role: STUDY_CHAIR
References:
citation: Hasenfuss G, Gustafsson F, Kaye D, Shah SJ, Burkhoff D, Reymond MC, Komtebedde J, Hunlich M; Reduce LAP-HF Trial Investigators. Rationale and Design of the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (Reduce LAP-HF) Trial. J Card Fail. 2015 Jul;21(7):594-600. doi: 10.1016/j.cardfail.2015.05.008. Epub 2015 Jun 6.
citation: Hasenfuss G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F, Malek F, Van der Heyden J, Lang I, Petrie MC, Cleland JG, Leon M, Kaye DM; REDUCE LAP-HF study investigators. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. Lancet. 2016 Mar 26;387(10025):1298-304. doi: 10.1016/S0140-6736(16)00704-2.
citation: Kaye DM, Hasenfuss G, Neuzil P, Post MC, Doughty R, Trochu JN, Kolodziej A, Westenfeld R, Penicka M, Rosenberg M, Walton A, Muller D, Walters D, Hausleiter J, Raake P, Petrie MC, Bergmann M, Jondeau G, Feldman T, Veldhuisen DJ, Ponikowski P, Silvestry FE, Burkhoff D, Hayward C. One-Year Outcomes After Transcatheter Insertion of an Interatrial Shunt Device for the Management of Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2016 Dec;9(12):e003662. doi: 10.1161/CIRCHEARTFAILURE.116.003662.
citation: Wolsk E, Kaye D, Borlaug BA, Burkhoff D, Kitzman DW, Komtebedde J, Lam CSP, Ponikowski P, Shah SJ, Gustafsson F. Resting and exercise haemodynamics in relation to six-minute walk test in patients with heart failure and preserved ejection fraction. Eur J Heart Fail. 2018 Apr;20(4):715-722. doi: 10.1002/ejhf.976. Epub 2017 Sep 26.
citation: Kaye DM, Petrie MC, McKenzie S, Hasenfubeta G, Malek F, Post M, Doughty RN, Trochu JN, Gustafsson F, Lang I, Kolodziej A, Westenfeld R, Penicka M, Rosenberg M, Hausleiter J, Raake P, Jondeau G, Bergmann MW, Spelman T, Aytug H, Ponikowski P, Hayward C; REDUCE LAP-HF study investigators. Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction. ESC Heart Fail. 2019 Feb;6(1):62-69. doi: 10.1002/ehf2.12350. Epub 2018 Oct 11.
citation: Wessler J, Kaye D, Gustafsson F, Petrie MC, Hasenfubeta G, Lam CSP, Borlaug BA, Komtebedde J, Feldman T, Shah SJ, Burkhoff D; REDUCE-LAP-HF Trial Investigators and Advisors. Impact of Baseline Hemodynamics on the Effects of a Transcatheter Interatrial Shunt Device in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2018 Aug;11(8):e004540. doi: 10.1161/CIRCHEARTFAILURE.117.004540.
citation: Hanff TC, Kaye DM, Hayward CS, Post MC, Malek F, Hasenfubeta G, Gustafsson F, Burkhoff D, Shah SJ, Litwin SE, Kahwash R, Hummel SL, Borlaug BA, Solomon SD, Lam CSP, Komtebedde J, Silvestry FE; REDUCE LAP-HF study investigators, and research staff. Assessment of Predictors of Left Atrial Volume Response to a Transcatheter InterAtrial Shunt Device (from the REDUCE LAP-HF Trial). Am J Cardiol. 2019 Dec 15;124(12):1912-1917. doi: 10.1016/j.amjcard.2019.09.019. Epub 2019 Sep 26.
citation: Obokata M, Reddy YNV, Shah SJ, Kaye DM, Gustafsson F, Hasenfubeta G, Hoendermis E, Litwin SE, Komtebedde J, Lam C, Burkhoff D, Borlaug BA. Effects of Interatrial Shunt on Pulmonary Vascular Function in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2019 Nov 26;74(21):2539-2550. doi: 10.1016/j.jacc.2019.08.1062.