FORWARD PRO Study
Research type
Research Study
Full title
FORWARD PRO study
IRAS ID
239180
Contact name
Jiske Simons
Contact email
Sponsor organisation
Medtronic
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
TBC, Will be registered on clinicaltrials.gov in Jan 2018
Duration of Study in the UK
7 years, 0 months, 26 days
Research summary
Summary of Research
To evaluate the acute and long term clinical performance and safety of Evolut™ PRO in a routine hospital setting and followed according to the approved intended use in local geography.The patients being treated in this study have symptomatic native aortic valve stenosis or a stenosed,insufficient, or combined surgical bioprosthetic valve failure necessitating valve replacement.
Summary of Results
Disposition of subjects A total of 638 subjects with symptomatic severe aortic stenosis or aortic bioprosthesis failure were enrolled at 39 sites in 14 countries in EMEA. TAVR using the Evolut PRO valve was attempted in 629 subjects and implanted in 610 (97%). At 5 years, 268 of the attempted implant subjects had died and 70 exited the study for various reasons, leaving a total of 291 implanted patients expected at the 5-year follow-up visit.Subject compliance
Subjects had follow-up from 30 days from index procedure until 5 years. Compliance was > 97% for each of the required follow-up visits. Compliance to required evaluations at follow-up visits varied with evaluation type, with the rate for TTE declining over the study period from 96.7% at baseline, 96.5% at discharge, 80.7% at 1-year, 61.0% at 3-year and 52.2% at 5-yearFor other required follow-up evaluations (NYHA, EQ-5D and Modified Rankin Score), rates remained more consistent and at 5-year visit were > 91% for each evaluation type.Clinical Investigation Plan deviations
A total of 1587 protocol deviations that were unrelated to Covid-19 were reported in 553 subjects in the attempted implant subjects. Most of these deviations were due to incomplete study assessment / data collection (34%) and CIP reportable events that were not reported per requirements (33%). Additionally, 77 protocol deviations that were Covid-19 related were reported in 68 subjects that underwent an attempted implant. Most of these deviations
(71%) were due to incomplete study assessment/data collection, and of these 93% occurred in the 3-year follow-up window. Although the deviations do not significantly impact our ability to perform relevant analyses, our longer-term echocardiographic (echo) results may be limited by the follow-up data collection and completion.Baseline characteristics
Patients who underwent an attempted implant were 61.8% female,had mean age of 81.7 years and a mean STS score of 4.7%, 91.5% were in NYHA class II or III, and 33.6% were frail.Primary endpoint
All-cause mortality at 30 days was 3.2% (20/629) with a one-sided upper 95% confidence interval of 4.6%, which was significantly less than the pre-specified performance goal of 5.5%.Secondary endpoints
A total of 335 subjects (59.2%) had none or trace total aortic regurgitation at discharge with a two-sided 95% confidence interval of 55.1 – 63.2%, which was insufficient to reject the null hypothesis of none or trace total aortic regurgitation ≥67.1%. The secondary objective was not met.The VARC-2 composite endpoint at 30 days included 104 events in 62 patients for a K-M rate 9.9%. At 5 years, the endpoint included 428 events in 307 subjects, for a K-M rate of 52.5%.
Additional safety data
At 5 years, the K-M rate was 45.6% for all-cause mortality, 28.6% for cardiovascular death, 48.3% for the composite of all-cause mortality or disabling stroke, 9.1% for disabling stroke, 3.8% for non-disabling stroke, and 8.5% for major bleeding. A total of 7 incidences of valve related dysfunction occurred in 7 patients that required reintervention.Hemodynamic performance
Mean aortic gradient decreased from 43.0 ± 16.0 mmHg at baseline to 7.9 ± 4.7 mmHg at discharge, and effective orifice area increased from 0.76 ± 0.27 cm2 at baseline to 2.09 ± 0.61cm2 at discharge.
Excellent rates were maintained through 5 years, with mean gradient of 9.0 ± 6.3 mmHg and effective orifice area of 2.0 ± 0.6 cm2.The proportion of subjects with none or trace total aortic regurgitation at discharge did not meet the prespecified performance, but an increasing trend over time was observed in patients that had available echos. At 5 years 85.2% of these subjects had none or trace AR. Similarly, an increasing trend in the proportion of subjects with none or trace PVL was also observed. In subjects with paired echos at all time points the proportion with none or trace PVL went from 66.7% at discharge to 91.6% at 5 years.
Functional status and quality of life
Most subjects that had an attempted implant showed improvement of NYHA scores. At 30 days 92% of surviving patients were in NYHA class 1 or II. At 5 years, 85.3% of survivors were in these classes, and 65.5% still showed improvement of ≥ one class.
The EQ-5D index score showed improvements from 0.68 ± 0.25 at baseline to 0.76 ± 0.25 at 30-day and 0.71 ± 0.26 at 1-year follow-ups but declined to 0.65 ± 0.29 at 3 years and to 0.62 ± 0.29 at 5 years.
The EQ-VAS score improved from 59.4 ± 19.3 at baseline to 67.4 ± 19.1 at 30 days, and remained higher than baseline at all consecutive timepoints, with a score of 62.9 ± 19.4 at 5 years.Conclusion:
Results from the FORWARD PRO study demonstrated efficacy and safety with the Evolut™ PRO bioprosthesis in elderly patients with symptomatic severe aortic stenosis at high or intermediate surgical risk. The low 30-day mortality rate of 3.2% was significantly lower than the performance goal, and safety outcomes were acceptable through 5 years in this mostly octogenarian, intermediate surgical risk population. Total aortic regurgitation at discharge was insufficient to reject the null hypothesis, but this dataset supports the efficacy of the Evolut™ PRO bioprosthesis in restoring aortic valve hemodynamic performance with low mean gradients maintained through 5 years of follow-up and improvements in PVL over time. The majority of patients improved in symptoms from aortic valve stenosis following the Evolut™ PRO implantation as assessed by NYHA classification and Quality of Life questionnaires.REC name
HSC REC A
REC reference
18/NI/0011
Date of REC Opinion
5 Feb 2018
REC opinion
Favourable Opinion