Overview of the BASIL-3 Trial

To determine which of the following is the most clinically- and cost-effective endovascular revascularisation treatment strategy for severe limb ischaemia secondary to femoro-popliteal disease:

1. Plain balloon angioplasty +/- bail-out bare metal stent
2. Drug-coated balloon +/- bail-out bare metal stent
3. Primary stenting with a drug-eluting stent

BASIL-3 is an individually randomised, multi-centre, pragmatic, three-arm, open label trial of three alternative revascularisation strategies for the management of SLI due to femoro-popliteal disease, incorporating a within-trial economic evaluation and permission for data collection for a subsequent prospective cohort study. BASIL-3 has been closely based on the currently HTA-funded BASIL-2 trial and will utilise the experience and expertise thereby gained by the Chief (CI) and Principal Investigators (PIs).

Severe limb ischaemia patients usually require frequent health care interventions in primary and secondary care after their primary revascularisation. To fully capture this activity, as well as the associated changes in QoL and health resource usage, patients will be closely followed up, especially during the first 12 months after randomisation.

Basil-3 will recruit 861 patients with severe limb ischemia due to femoro-popliteal disease from England, Wales, Scotland, and possibly other EU states over 36 months. Patients will be followed up for an average of just over 3 years after their intervention.

Patients will be randomised, to have either a Plain Balloon Angioplasty with a Bare Metal Stent (if needed) or Drug Coated Balloon with a Bare Metal Stent (if needed) or a Drug Eluting Stent.

Recovery time from endovascular intervention is often prolonged and caring for patients with SLI is extremely costly to NHS and social care services, so patients will be asked to complete questionnaires on their quality of life, attitudes to their life, and the personal impact upon their finances. Wider financial impact will be assessed via a Health Economic Analysis.

Recruitment is anticipated to take place at approximately 60 vascular centres; 50 in England, 5 in Scotland, and 5 in Wales. 

Any patients over the age of 18 with a diagnosis of severe limb ischaemia due to femoro-popliteal disease and who, in the opinion of the multi-disciplinary team, require early vascularisation.

The allocated intervention (DCB+/- bail-out BMS first’ or a ‘DES first’ or a ‘PBA +/-bail-out BMS first’) should be scheduled within two weeks of the date of randomisation where possible and clinically appropriate.

For all randomised patients, in the great majority of cases, regardless of the exact technique / devices being used, the procedure will be performed under local anaesthesia via an ultrasound-guided puncture of the common femoral artery; occasionally intravenous sedation may be given and, rarely, a general anaesthetic may be required. Success will be established by, palpation of foot pulses and measurement of ABPI /TBPI. Copies of intra-operative imaging will be sent for centralised Bollinger scoring and independent, blinded adjudication of technical success and run-off.

All trial devices must be CE marked and come from general hospital stock and none of the physical components of the intervention are supplied by the BASIL-3 Trial Office. All components should be stored in accordance with local standard procedures.

The brand name, type, and reference code must be recorded for all trial-related components i.e. type of balloon or stent, active drug incorporated into the device (where applicable).

Primary Outcome Measure

Amputation free survival, AFS, defined as the time to major limb (above the ankle) amputation of the index (trial) limb or death from any cause.

Secondary Outcome Measures

• Overall Survival
• Major Adverse Limb Events (MALE), defined as amputation (transtibial or above) or any major vascular re-intervention (thrombectomy, thrombolysis, BA, stenting, or surgery)
• In-hospital and 30-day morbidity and mortality
• Major cardiovascular events (SLI and amputation affecting the contralateral limb, ACS, stroke)
• Relief of ischaemic pain (VAS, medication usage)
• QoL using generic (EQ-5D-5L, SF-12,) and disease specific (VascuQoL) tools
• Re- and cross-over intervention rates
• Healing of tissue loss (ulcers, gangrene) as assessed by the PEDIS and the WiFi  scoring      and classification systems
• Extent and healing of minor (toe and forefoot) amputations (also using PEDIS and WiFi)
• Haemodynamic changes; absolute ankle and toe pressures, ABPI, TBPI.

Between Jan 29, 2016, and Aug 31, 2021, 481 participants (167 [35%] women) of mean age 71.8 years were randomised.Major amputation or death occurred in 106 of 160 (66%) participants in the PBA +/- BMS group, 97 of 161 (60%) participants in the DCBA +/- BMS, and 93 of 159 (58%) participants in the DES group.

The adjusted hazard ratios were:

• PBA +/- BMS vs DCBA +/- BMS: 0.84 (97.5% confidence interval, CI: 0.61 to 1.16), p=0.22;
• PBA +/- BMS vs DES: 0.83 (97.5% CI: 0.60 to 1.15), p=0.20).

There were no differences in SAEs between the groups.

Conclusion

In the BASIL-3 trial the use of drug coated balloons and drug eluting stents in the femoro-popliteal segment did not confer clinical benefit over the use of plain balloons and bare metal stents.