The CONFIDENCE Registry
Research type
Research Study
Full title
CONFIDENCE (Controlled delivery for improved outcomes with clinical evidence) Registry
IRAS ID
246628
Contact name
Philip MacCarthy
Contact email
Sponsor organisation
Abbott Medical
Clinicaltrials.gov Identifier
n/a, n/a
Duration of Study in the UK
2 years, 7 months, 30 days
Research summary
Summary of Research
The registry is intended to characterise clinical safety and device performance from experienced transcatheter aortic valve implantation (TAVI) (a non-surgical alternative to open heart surgery), centres in Europe that use Portico™ valve, delivery system and loading systems to treat patients with severe aortic stenosis (the narrowing of the aortic valve opening, due to a build-up of calcium which restricts the blood flow from the left ventricle, one of the four chambers of the heart, to the aorta, the main artery of the body supplying oxygenated blood to the circulatory system).
The study is a prospective, non-randomised, observational, single-arm, multicentre registry of patients clinically indicated for implantation of a Portico™ transcatheter aortic heart valve.
Study visits are baseline, index procedure, pre-discharge, 30 days, 12 months. About 60 patients will be recruited at 3-5 centres in the UK.
Patients that meet the inclusion criteria and do not meet any of the exclusion criteria and are clinically indicated for implantation of the Portico™ transcatheter aortic heart valve will be eligible to be enrolled into the study.
The study will only look to collect 'standard of care' clinical and device performance data of the Portico™, delivery system and loading system to treat patients with aortic stenosis.
Summary of Results
The Portico™ self-expanding, repositionable transcatheter aortic heart valve implantation (TAVI) system has been CE Marked since 2012. Despite growing acceptance of the Portico TAVI system in Europe, the amount of published real-world clinical evidence remains limited. Currently, the majority of multicenter publications describing outcomes with the Portico valve are based on the results of pre-market and mandated post-approval (PMCF) studies. The 30-day outcomes from the Pre-CE Mark Study (Portico TF EU) with 222 subjects were published in August 2017 and the 1-year data from the same cohort was published in February 2018. A longer-term follow-up study of the Portico valve was required as a condition of CE Mark, which is being fulfilled by the Portico I study. The Portico I study completed enrollment in 2017 with the 30-day outcomes first published in July 2018 and 1-year data published later that year. As Portico I represents early experience with the valve, the CONFIDENCE Registry was initiated to evaluate outcomes as implanters have since gained experience with the Portico valve and are now using the new FlexNav™ delivery system (DS). This Final Report describes the complete 30-day outcomes and 1-year survival from the CONFIDENCE Registry.
The CONFIDENCE Registry (NCT03752866) was designed to assess the procedural safety and device performance of the Portico valve from experienced TAVI centers that commercially use the Portico valve to treat patients with severe aortic stenosis (AS). This was a prospective, non-randomized, observational, single-arm, multicenter registry of 1001 patients clinically indicated for implantation of a Portico transcatheter aortic heart valve. The study had broad inclusion criteria (symptomatic, degenerative severe aortic stenosis) and minimal exclusion criteria to ensure the results were generalizable to the broadest TAVI population. Upon CE Mark of the FlexNav DS, the protocol was updated to split enrollment in two even, sequential cohorts. The first cohort of 501 subjects were implanted from 25 October 2018 to 17 January 2020 using the first-generation Portico DS (i.e. GEN 1 cohort). The second cohort of 500 subjects was implanted with the FlexNav DS (i.e. FlexNav cohort); enrollment in this cohort started 9 March 2020 and was completed on 30 July 2021. There were 28 sites participating in this study from 9 countries: Australia, Belgium, Czech Republic, Germany, Italy, Poland, Spain, Switzerland and United Kingdom. Data were collected at baseline, procedure, discharge (or 7 days whichever occurred first), 30 days, and 12 months post index procedure (survival check only). Descriptive endpoints related to implant success, safety outcomes, valve performance, cardiac symptoms and quality of life were assessed at 30 days along with mortality through 12 months.
The average age of subjects enrolled in the CONFIDENCE Registry was 82.0 years, 62.5% female, the average STS PROM score was 4.2%, and the average EuroSCORE II was 4.8%. Additional risk factors of frailty (45.4% of subjects had at least 1 frailty factor), chronic kidney disease (26.9%) and chronic lung disease (20.2%) were also present in this study. The most commonly reported medical conditions were hypertension (87.0%), mitral valve disease (61.3%), dyslipidemia (61.8%) and coronary artery disease (55.1%).
Procedural success was high at 97.5%, with one case (0.1%) of procedural mortality reported and 1.9% of subjects requiring implantation of a second valve during the index procedure. The observed rate of 1.9% for requiring a second valve is in line with other larger, prospective studies that used the Portico valve and first-generation Portico DS (1.8-2.3%). Most (98.7%) of the subjects were implanted via transfemoral access.
All-cause mortality and disabling stroke rates at 30 days were within expected ranges for this population at 2.6% and 1.8% respectively. Individual VARC-2 safety event rates such as life-threatening bleeding (3.4%) and major vascular complications (7.3%), as well as new permanent pacemaker implantation (19.0%), were also within the ranges for competitor devices studied in a similar patient population, further supporting an acceptable safety profile of the Portico valve system.
The Portico valve demonstrated an excellent hemodynamic profile at 30 days with a mean transvalvular gradient of 7.09 ± 3.71 mmHg and aortic valve area of 1.82 ± 0.49 cm2. Paravalvular leak was categorized by an independent core lab as mild or less in 98.0% of subjects at 30 days with no cases of severe paravalvular leak reported.
At 1-year follow-up, Kaplan Meier (KM) estimated all-cause mortality was 12.3%.
In conclusion, high procedural success coupled with low rates of safety events and excellent hemodynamic function at 30 days supports the continued use of the Portico valve system as a safe treatment option for patients considered high surgical risk suffering from severe, symptomatic AS.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
18/YH/0373
Date of REC Opinion
9 Nov 2018
REC opinion
Further Information Favourable Opinion