BASIL Investigators Meeting Vascular Society Manchester 1 December 2016

Transcription

1 BASIL Investigators Meeting Vascular Society Manchester 1 December 2016

2 BASIL Introduction and Overview Professor Andrew Bradbury Chief Investigator

3 BASIL Trials Overview Severe Limb Ischaemia (SLI) (RP +/- TL) Correct inflow disease (endo > open) FP disease Life expectancy (years) / vein? IP disease BASIL-2 > 2 and yes Vein bypass BASIL-1 PBA +/- BMS < 2 and / or no BASIL-3? DES? DCB+/- BMS Vein bypass? BET BASIL REGISTRY

4 BASIL-2 infra-popliteal (IP) SLI Vein Bypass first (n = 300) Best Endovascular Treatment first (n = 300) BASIL-3 femoro-popliteal (FP) SLI PBA +/- BMS (n = 282) DCB +/- BMS (n = 282) DES (n = 282) Follow-up months Amputation free survival Overall Survival Clinical end-points Quality of revascularisation Quality of life Functional status Health economic

5 BASIL 2/3 Co-applicants Southampton (Professor Shearman, Dr Odurny) St George s (Mr Hinchliffe and Professor Belli) Imperial (Professor Davies, Dr Burfitt) Oxford (Mr Perkins, Dr Uberoi) Birmingham / WM (Mr Claridge, Dr Ganeshan) Leicester (Professor Naylor, Dr Adair) Hull (Professor Chetter, Professor Ettles) Leeds (Professor Scott, Dr Patel) Sheffield (Professor Beard, Dr Cleveland) Newcastle (Professor Stansby, Dr Jackson) Scotland (Professor Brittenden, Dr Yadavaldi) VSGBI BSIR ESVS CF Diabetes-UK

6 BASIL-3 BASIL Agenda Recruitment and centres Excluded devices / XS treatment costs BASIL-2 Building the case for equipoise PI Survey Follow-up Recruitment so far Between now and 8 March 2017 Perspective form the TSC QuinteT

7 BASIL 3 Up-date Dr Benjamin Hunt BASIL-3 Trial Co-ordinator

8 Jan-16 Feb-16 Mar-16 Apr-16 May-16 Jun-16 Jul-16 Aug-16 Sep-16 Oct-16 Nov-16 Number of Patients BASIL-3 Monthly Recruitment Pilot Disappointingly, despite more centres being open, we have dropped below target (for the first time) in October and November Month Target Actual Cumulative

9 01/11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/ /11/2016 BASIL-3 Recruitment November November rescued by 5 patients at HEFT in 3 days but still 3 short for the month Projected Actual

10 Jan-16 Feb-16 Mar-16 Apr-16 May-16 Jun-16 Jul-16 Aug-16 Sep-16 Oct-16 Nov-16 Dec-16 Jan-17 Number of Patients BASIL-3 Pilot Phase Target 100 by end January Recruitment down in September, October and November why? Month Projected Recruitment Target Pilot Recruitment Actual recruitment

11 Number of Patients Jan-16 BASIL-3 Overall Recruitment Feb-16 Mar-16 Apr-16 May-16 Jun-16 Jul-16 Aug-16 Sep-16 Oct-16 Nov-16 Dec-16 Jan-17 Feb-17 Mar-17 Apr-17 May-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Jan-18 Feb-18 Mar-18 Apr-18 May-18 Jun-18 Jul-18 Aug-18 Sep-18 Oct-18 Nov-18 Dec-18 Jan Monthly recruitment targets November 16 December 18 January 19 February 20 March 21 April 22 May 23 June, July, August 24 September 36, until January / month N = January Month Projected Recruitment Target Recruitment Target Pilot Recruitment Actual recruitment

12 BASIL-3 Recruitment Centres Open Leeds * Edinburgh * Frimley Park * Recently opened United Lincolnshire Newcastle UHNM Basildon Imperial North Durham Nottingham Colchester General Royal Oldham Royal Cornwall North Cumbria Aspiration is 50+ UK centres About 15 / centre / 2 years Russell's Hall East Kent Sheffield Royal Gwent Dorset County Heartlands

13 BASIL-3 XS Treatment Costs (c. 500K)

14 BASIL-3 Discussion Questions Comments Concerns Suggestions

15 BASIL-2 The case for equipoise PI Survey (June 2016) Follow-up HRQL booklets Recruitment so far Between now and 8 March 2017 Perspective from the TSC QuinteT

16 BASIL-2 - building the case for equipoise Mr Mathew Popplewell BASIL-2 Research Fellow

17 Why B-2? Why do we need BASIL-2 when it is obvious that endovascular revascularisation is the best strategy for almost all patients requiring infra-popliteal intervention for SLI? (i.e. reserve surgery for endoimpossibles and endo-failures )

18 Reason 1: in BASIL-1 bypass after endo-failure was much less successful than primary bypass So, endovascular is not a free shot Amputation free survival Overall survival Bypass first Bypass first Bypass after angioplasty Bypass after angioplasty

19 Reason 2: In BASIL-1, although IP vein bypass (VB) and IP plain balloon angioplasty (PBA) were similar in terms of amputation free survival (AFS) Amputation free survival P = 0.1 Vein bypass PBA HR=0.68, 95% CI: , p=0.1

20 IP VB was better (p = 0.06) than IP PBA in terms of overall survival HR=0.60, 95% CI: D18% Overall survival Vein bypass P = 0.06 PBA D22% What about new technology?

21 Statistical Interpretation Whilst neither result meets standard criteria for statistical significance, the direction of the effect favours VB and the confidence intervals rule out the possibility of clinically important effects in favour of PBA * *Popplewell MA, Davies MA, Narayanswami J, Renton M, Sharp A, Patel SA, Bate G, Deeks JD, Bradbury AW. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: a comparison of outcomes in patients with infra-popliteal disease randomised to vein bypass or plain balloon angioplasty. Currently under revision.

22 Reason 3: Current clinical outcomes following IP endovascular intervention are no better than in B-1 Despite fewer technical failures, AFS and OS after IP endovascular intervention in our unit (HEFT) are currently ( ) no better than those observed in BASIL-1 ( ) P = 0.3 Amputation free survival Overall Survival P = 0.2

23 Reason 4: Contemporary ( ) IP vein bypass is significantly better than IP angioplasty Overall survival IP vein bypass AF Survival IP vein bypass IP angioplasty P = IP angioplasty P = 0.026

24 Conclusions In BASIL-1, bypass after failed PBA was much less successful than primary bypass (AFS / OS) In BASIL-1, IP outcomes rule out the possibility of clinically important effects in favour of PBA Contemporary IP best endovascular treatment (BET) at HEFT is not more clinically successful than IP PBA in BASIL-1 (AFS / OS) Outside trial, at HEFT, contemporary IP VB is superior to BET (AFS p = 0.026, OS p = 0.007)

25 Guy s and St Thomas, London 279 limbs, 243 patients Propensity scoring 125 matched legs in the IP endovascular and bypass groups Patency and AFS better after bypass Limb salvage similar More complications and longer hospital stay after bypass

26 Patency

27 Limb salvage and AFS

28 Circulation: Cardiovascular Intervention 2016 Largest ever meta-analysis of IP endovascular intervention 6769 patients, 9399 BK lesions, 97% patients had SLI 63% in European centres 75% DM, 75% hypertension, 53% hyperlipidaemia 91% immediate technical success rate; 9% required stenting Conclusions Contemporary studies of PTA in infrapopliteal arteries report suboptimal short-term and 1-year clinical outcomes Large, multicentre, prospective studies evaluating IP treatment modalities are essential to advance uniform treatment standards

29 Why B-2? Because, there is no evidence to support endovascular intervention as the preferred treatment for SLI due to IP disease in patients who can have vein distal bypass Indeed, what limited data we have suggest endovascular is unlikely to be better and should usually be reserved for those who cannot have distal vein bypass

30 Conclusions Academically, there is no reason to discontinue BASIL-2 as it remains an important question with very broad support (UK, Europe, US) But, there are obviously barriers to recruitment Highly variable patient pathways and management between UK centres despite: same patients same evidence base (or lack of it) same NHS resources Why should this be?

31 BASIL-2 PI survey Mr Hugh Jarrett Senior Trial Co-ordinator

32 Aim to explore reasons for under-recruitment Research question no longer important? Lack of equipoise? Patient refusal? Logistical barriers? Lack of research nurses? Burden of data collection? Lack of theatre time? Insufficient skills endo/bypass? Competition with other trials? Influence of industry?

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34 Survey Results Factor influencing low accrual % Agreeing ( 5 on 1-10 scale) Equipoise in the MDT 79.3 Patient treatment preferences 58.5 Scheduling theatre time 34.3 Lack of research nurses 31.0* Data burden 24.1 Insufficient skills for bypass 10.3 Insufficient skills for angioplasty 6.8 Competition with other trials 3.4 *This is the only question which had a response of 10; completely prevents accrual

35 Please indicate the degree to which the following are negatively impacting upon recruitment, in your opinion

36 Please indicate the degree to which the following are negatively impacting upon recruitment, in your opinion

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38 Research question no longer important? NO NO new evidence / trials / guidelines (NICE) PI s remain 100% supportive of question Virtually the whole of UK vascular / endovascular surgery signed up, growing international interest Current evidence indicates very considerable ongoing uncertainty as to whether IP endovascular intervention is more clinically and cost-effective than bypass in patients who can have both Indeed, what data we have suggest endovascular should be reserved for those that cannot have distal vein bypass

39 BASIL-2 follow-up Mr Gareth Bate Senior Research CNS

40 BASIL-2 follow-up

41 BASIL-2 follow-up Complete and timely return of HRQL booklets is absolutely vital please because: Time sensitive PROMS (quality of revascularisation) by far most important outcome Health economic analysis

42 Recruitment so far Between now and 8 March 2017 Professor Andrew Bradbury Chief Investigator

43 B-2 Centres UK = 50 Sweden = 1 Denmark = 1

44 BASIL-2 Recruitment As of , 168 patients, 2 in November

45 Where is recruiting? 52 centres open, 35 (69%) have recruited York Need each Southmead (Bristol) Kent and Canterbury centre to Southampton General Hospital randomise Doncaster Royal Infirmary Colchester Royal Sussex Addenbrookes Leicester Royal Infirmary Frimley Park Hospital Northern General Hospital Pilgrim Hospital Freeman Hospital St Georges Hospital Royal Gwent Hospital Russells Hall Hospital Hull Royal Infirmary St Thomas' Hospital patients (by end 2018) (hard to believe that s not possible)

46 Thank you Denmark (6 in 8 months)! Why are things so very different in Denmark?

47 Where should we be? Need another 432 patients (8 / centre) by the end of 2018 (25 months) Do we still need to randomise 600 patients?

48 B2 Outcomes AFS (n = 162) AFS OS very similar to that predicted by BASIL-1 analysis and used to inform the power calculation So, yes, 600 patients probably needed 63% at 2 years OS 73% at 2 years 432 to go!

49 Can we do it? Yes, we can!!! 432 patients to go 52 centres 8 patients per centre Recruitment ends 31 December 2018 = 25 months to go patients per month So, that is one patient randomised about every three months at each centre Hard to believe that is not possible!!!

50 Aug-14 Oct-14 Dec-14 Feb-15 Apr-15 Jun-15 Aug-15 Oct-15 Dec-15 Feb-16 Apr-16 Jun-16 Aug-16 Oct-16 Dec-16 Feb-17 Apr-17 Jun-17 Aug-17 Oct-17 Dec-17 Feb-18 Apr-18 Jun-18 Aug-18 Oct-18 Dec-18 Feb-19 Apr-19 Jun-19 Aug-19 Oct-19 Dec-19 Feb-20 Apr-20 Jun-20 Between now and 7 March Target after September 2015 Monitoring Meeting Projection Target Recruitment Actual Recruitment Revised accrual Current rate Best rate N = patient / month No cost extension N = 600 Previous trajectory Need 250 by end February 2017 to stay alive 82 to go!!! 1.58 patients per centre over 3 months 50 August 2017 End

51 Can we do it yes we can! Surely????

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53 Thank you