Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.,The Lancet

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Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.
The Lancet ( IF 98.4 ) Pub Date : 2020-06-25 , DOI: 10.1016/s0140-6736(20)31358-1
Raj R Makkar ₁ , Wen Cheng ₁ , Ron Waksman ₂ , Lowell F Satler ₂ , Tarun Chakravarty ₁ , Mark Groh ₃ , William Abernethy ₃ , Mark J Russo ₄ , David Heimansohn ₅ , James Hermiller ₅ , Stephen Worthley ₆ , Bassem Chehab ₇ , Mark Cunningham ₈ , Ray Matthews ₈ , Ravi K Ramana ₉ , Gerald Yong ₁₀ , Carlos E Ruiz ₁₁ , Chunguang Chen ₁₂ , Federico M Asch ₁₃ , Mamoo Nakamura ₁ , Hasan Jilaihawi ₁₄ , Rahul Sharma ₁₅ , Sung-Han Yoon ₁ , Augusto D Pichard ₁₆ , Samir Kapadia ₁₇ , Michael J Reardon ₁₈ , Deepak L Bhatt ₁₉ , Gregory P Fontana ₂₀

Affiliation

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Washington Hospital Center, Washington, DC, USA.
Mission Health and Hospitals, Asheville, NC, USA.
Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA; Newark Beth Israel Medical Center, Newark, NY, USA.
St Vincent Heart Center, Indianapolis, IN, USA.
Royal Adelaide Hospital, Adelaide, SA, Australia; Genesis Care, Sydney, NSW, Australia.
Cardiovascular Research Institute of Kansas, Ascension Via Christi Hospital, Wichita, KS, USA.
University of Southern California, Los Angeles, CA, USA.
Advocate Christ Medical Center, Oak Lawn, IL, USA; Heart Care Centers of Illinois, Palos Park, IL, USA.
Fiona Stanley Hospital, Murdoch, WA, Australia.
Hackensack University Medical Center, Hackensack, NJ, USA.
Newark Beth Israel Medical Center, Newark, NY, USA.
MedStar Health Research Institute, Washington, DC, USA.
NYU Langone Health, New York, NY, USA.
Stanford University Medical Center, Stanford, CA, USA.
Abbott, Abbott Park, IL, USA.
Cleveland Clinic, Cleveland, OH, USA.
Houston Methodist Hospital, Houston, TX, USA.
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Cardiovascular Institute, Los Robles Regional Medical Center, Thousand Oaks, CA, USA.

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%]; p_{non-inferiority}=0·034, p_superiority=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%]; p_{non-inferiority}=0·0058, p_superiority=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.

中文翻译：

具有严重主动脉瓣狭窄的高危和极高风险患者的自扩张瓣膜内瓣膜瓣膜瓣膜瓣瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣膜瓣环瓣膜瓣膜瓣膜瓣外瓣膜栓塞术（PORTICO IDE）

背景

需要随机试验数据来评估自膨胀瓣膜内门廓门导管主动脉瓣膜系统（美国明尼苏达州圣保罗的Abbott Structural Heart）与任何市售瓣膜相比的安全性和有效性，以比较设计之间的性能。

方法

在这项前瞻性，多中心，非自卑性，随机对照试验（门廓可再穿鞘式主动脉瓣系统美国研究器械豁免试验[PORTICO IDE]）中，从52个医疗中心招募了具有严重症状性主动脉瓣狭窄的高危和高危患者在美国和澳大利亚从事经导管主动脉瓣置换的经验丰富。如果患者年龄在21岁或以上，纽约心脏协会功能性II级或更高且患有严重的自然主动脉瓣狭窄，则符合条件。符合条件的患者采用置换区组随机分配（区组大小为2和4）随机分配（1：1），并按临床研究部位，手术风险队列和血管通路方法进行分层，用第一代Portico瓣膜和输送系统或市售瓣膜（环内球囊扩张式Edwards-SAPIEN，SAPIEN XT或SAPIEN 3瓣膜[Edwards LifeSciences，Irvine，CA，美国]进行经导管主动脉瓣置换。或环形上自膨胀CoreValve，Evolut-R或Evolut-PRO阀[Medtronic，明尼阿波利斯，美国明尼苏达州]。研究现场工作人员，植入医师和研究参与者均未接受治疗分配。核心实验室和临床事件评估者被掩盖了治疗分配。主要的安全终点是30天时全因死亡率，致残性中风，需要输血的危及生命的出血，需要透析的急性肾损伤或主要血管并发症的复合物。主要功效终点为1年时的全因死亡率或致残性中风。术后2年内评估临床结局和瓣膜性能。主要分析是按意向治疗，Kaplan-Meier方法是估计事件发生率。主要安全性的非劣效性边界为8·5％，主要功效终点的非劣性性边界为8·0％。该研究已在ClinicalTrials.gov注册，NCT02000115，并且正在进行中。

发现

在2014年5月30日至9月12日之间，以及2015年8月21日至2017年10月10日之间，由于出资者暂停招聘11个月，我们招募了1034位患者，其中750位合格并随机分配到Portico瓣膜组（n = 381）或商用阀组（n = 369）。平均年龄为83岁（SD 7），其中395例（52·7％）患者为女性。对于30天的主要安全性终点，Portico瓣膜组的事件发生率高于商用瓣膜组（52 [13·8％] vs 35 [9·6％]；绝对差异4·2、95％ CI -0·4至8·8 [上限置信度{UCB} 8·1％]； p_非劣效性= 0·034，p_优劣= 0·071）。1年时，各组的主要疗效终点发生率相似（Portico组为55 [14·8％]与之相比，商用阀组为48 [13·4％]；相差1·5％，95％CI -3·6至6·5 [UCB 5·7％]；p_非劣等= 0·0058，p_优势= 0·50）。在2年时，死亡率（80 [22·3％]对70 [20·2％]； p = 0·40）或致残性中风（10 [3·1％]对16 [5·0％]； p = 0·23）组之间相似。