TY - JOUR
T1 - Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE)
T2 - a randomised, controlled, non-inferiority trial
AU - Makkar, Raj R.
AU - Cheng, Wen
AU - Waksman, Ron
AU - Satler, Lowell F.
AU - Chakravarty, Tarun
AU - Groh, Mark
AU - Abernethy, William
AU - Russo, Mark J.
AU - Heimansohn, David
AU - Hermiller, James
AU - Worthley, Stephen
AU - Chehab, Bassem
AU - Cunningham, Mark
AU - Matthews, Ray
AU - Ramana, Ravi K.
AU - Yong, Gerald
AU - Ruiz, Carlos E.
AU - Chen, Chunguang
AU - Asch, Federico M.
AU - Nakamura, Mamoo
AU - Jilaihawi, Hasan
AU - Sharma, Rahul
AU - Yoon, Sung Han
AU - Pichard, Augusto D.
AU - Kapadia, Samir
AU - Reardon, Michael J.
AU - Bhatt, Deepak L.
AU - Fontana, Gregory P.
N1 - Funding Information:
RRM has received research grants, speaker fees, and proctoring fees from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. GPF is a consultant for and has received proctoring fees from Abbott, Medtronic, and LivaNova; is a Structural Heart Advisory Board Member for Abbott; and is a principal investigator for Abbott and Medtronic. DLB has been on the advisory board for Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, and Regado Biosciences; has been on the Board of Directors for Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has been Chair of the American Heart Association Quality Oversight Committee; has been on Data Monitoring Committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial as Data Monitoring Committee Chair, funded by St Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, and Population Health Research Institute; has received honoraria from the American College of Cardiology, Baim Institute for Clinical Research, Belvoir Publications, Duke Clinical Research Institute, HMP Global, Journal of the American College of Cardiology, Medtelligence ReachMD, Level Ex, MJH Life Sciences, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, WebMD, Clinical Cardiology, National Cardiovascular Data Registry-ACTION Registry Steering Committee, and Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Research and Publications Committee; has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Eli Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, and The Medicines Company; has received royalties from Elsevier; has been a site co-investigator for Biotronik, Boston Scientific, Cardiovascular Systems, St Jude Medical (now Abbott), and Svelte; has been a trustee for American College of Cardiology; and has done unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. HJ has been a consultant for Abbott, Boston Scientific, and Medtronic; and has received grant support from Abbott, Edwards Lifesciences, Medtronic, and Heart Leaflet Technologies. TC is a consultant for Edwards LifeSciences, Medtronic, Abbott, and Boston Scientific. RW on the Advisory Board for Amgen, Boston Scientific, Cardioset, Cardiovascular Systems, Medtronic, Philips, and Pi-Cardia; is a consultant for Amgen, Biotronik, Boston Scientific, Cardioset, Cardiovascular Systems, Medtronic, Philips, and Pi-Cardia; has received grant support from AstraZeneca, Biotronik, Boston Scientific, and Chiesi; is on speakers' bureaus for AstraZeneca and Chiesi; and is an investor in MedAlliance. RKR has received speaker, consulting, and proctoring fees from Edwards Lifesciences; consulting fees from Abbott and Medtronic; and research support from Boston Scientific. FMA has no personal conflicts of interest to report; and reports institutional (MedStar Health) disclosures as director of an Academic Echocardiographic Core laboratory with institutional research contracts with Abbott, Edwards, Boston Scientific, Medtronic, Livanova, Biotronik, and Vascular Innovations. MJRe is a consultant for Medtronic. SW has received research grants from Abbott and Biotronik. GY is a physician proctor for Abbott Vascular. MG is an Advisory Board Member for Structural Heart Abbott. JH has received proctoring fees from Abbott. ADP is an employee of Abbott Structural Heart. MC has received personal fees from Abbott; is a consultant and received proctor and consultant fees from Medtronic; and is a consultant for Edwards Lifesciences. BC has received grant and personal fees from Abbott, and received personal fees from Edwards Lifesciences, Medtronic, and Boston Scientific. RM has received consulting and speaking fees from Medtronic; is a data safety monitoring board member for Abbott-sponsored trials; and is an investor in Foldax. All other authors declare no competing interests.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020
Y1 - 2020
N2 - Background: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. Methods: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. Findings: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI −0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI −3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. Interpretation: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. Funding: Abbott.
AB - Background: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. Methods: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. Findings: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI −0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI −3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. Interpretation: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. Funding: Abbott.
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U2 - 10.1016/S0140-6736(20)31358-1
DO - 10.1016/S0140-6736(20)31358-1
M3 - Article
C2 - 32593323
AN - SCOPUS:85087736790
JO - Journal of Cleaner Production
JF - Journal of Cleaner Production
SN - 0959-6526
ER -