A Community and Hospital cAre Bundle to improve the medical treatment of severe cLaudIcation and critical limb iSchaemia (CHABLIS)

Study design and regulatory approvals

The “Community and Hospital cAre Bundle to improve the medical treatment of cLaudIcation and critical limb iSchaemia” (CHABLIS) study was a prospective multicentre mixed methods study, delivered in four National Health Service (NHS) regions between September 2019 to 2021. The research was reviewed and approved by the NHS Wales Research Ethics Committee (reference 20/WA/0319) and NHS Health Research Authority (HRA). It was funded by the National Institute for Health Research NIHR Research for Patient Benefit (RfPB) programme (NIHR202008). It was prospectively registered on an online repository; the protocol and LEGS intervention constituents have been made available online (reference: ISRCTN13202085, free to access and use). The study was sponsored by the University of Leicester. Patients provided written informed consent before taking part. The funder had no input in study conduct or analyses.

Aim and objectives

The main aim was to assess the fidelity and feasibility of delivering the LEGS complex clinical intervention as part of the care of patients with symptomatic PAD referred to secondary care.

The first objective was to quantitatively assess the fidelity of delivering LEGS. The secondary objectives included assessing recruitment and retention rate to receiving PAD care based on the LEGS intervention. A formal qualitative assessment of the perceived acceptability of LEGS is presented separately¹².

Study population (inclusion criteria)

Individuals >18 years of age with severe IC or CLTI (Rutherford stages 3–6) referred to secondary care. Recruitment lasted six months (March 2021-September 2021) across:

-  Leicester Vascular Institute,

-  Guy’s & St Thomas’ NHS Foundation Trust,

-  University Hospitals Birmingham NHS Trust,

-  University Hospital of Coventry & Warwickshire NHS Trust.

Patients were recruited from inpatient wards on the day of admission and all outpatient clinics. The recruiting sites include patients from urban and rural backgrounds, providing vascular services 8.2 million.

Outcome measures

Primary outcome measure: Fidelity of LEGS intervention delivery.

Secondary outcome measures: Proportion of patients agreeing to take part out of those invited (intervention recruitment rate); proportion who provide data at end of follow-up (intervention retention rate); cardiovascular events; mortality; Body Mass Index (BMI); self-reported medication adherence [using the Brief Adherence Rating Scale¹³]; smoking status (self-reported); uptake of smoking-cessation services for smokers; cholesterol, low-/high-density lipoprotein levels.

Development of the LEGS intervention

Figure 1. Infographic detailing each element of the complex clinical intervention, which healthcare provider receives the relevant element, literature/evidence, and success criteria (outcome measures) for this study.

LEGS was developed prior to this study (Figure 1) based on co-creation principles¹⁴. A review of best available evidence and PAD guidelines identified 5 key treatment areas [PAD best medical therapy (BMT)]^3,10,15: Lipid control; antiplatelet therapy; Blood pressure (BP) control; smoking cessation; glucose control.

Following that, four workshops were held, involving 91 patients with CLTI, 24 with IC, four carers, 17 nurses, four general practitioners (GPs), and five surgeons, to examine barriers and facilitators of delivering BMT; based on these, a set of documents (printed and digital format) were created to address barriers and facilitate BMT.

LEGS intervention constituents

Inpatient healthcare professionals’ checklist

One-page checklist for patients admitted in a hospital setting. The list was checked initially with the first patient clerking (on admission) by the relevant HCP and then immediately before discharge.

Outpatient doctors’ checklist

One-page checklist for those seen in a clinic. It was developed with the help of clinic co-ordinators, GPs, nurses, and surgeons. It was used during consultation prompting the HCP to address all 5 PAD BMT areas.

Leaflet for patients and relatives

A lay leaflet with information aiming to support patients achieve BMT targets. The British Heart Foundation and Circulation Foundation PAD documents were used as a basis on which the patients’ helping us with the development pathway expanded as per their perceptions/preferences and most current BMT guidance^2,10. This was given to the patient upon presentation and mailed to the GP (available in five languages).

GP letter

A standardised letter with action points relating to BMT. This was developed by GPs in 11 different regions. The letter was sent to the GP after discharge and each clinic visit. This addressed the poor and confusing secondary care communications.

GP follow-up letter

A follow-up letter sent automatically to the GP four weeks after each contact with secondary care prompting action for BMT targets.

The intervention schematic and protocol (see Extended data) are available online (digital) free-of-charge.

Definitions and reporting

Definitions were as per the reporting standards of the Society for Vascular Surgery for PAD¹⁰. Reporting followed the “Strengthening the reporting of observational studies in epidemiology” guidance.

Follow-up procedures

-  Baseline; collection of clinical presentation information and cardiovascular risk-factors.

-  Assessment 1; day of discharge or clinic appointment. The number of the LEGS intervention components filled in correctly were recorded the.

-  Assessment 2; 15 days discharge or clinic appointment. The GP was contacted to assess whether they received and read the LEGS letter and followed advice regarding BMT.

-  Assessments 3 and 4; 30 days and six months. Participants were followed-up in person. Patients’ notes were reviewed alongside routine biochemistry performed at each visit. Prescriptions were obtained from patients and GPs.

Sample size calculations and statistical analysis

Based on our pre-study work with stakeholders (focus groups and surveys), we were willing to accept the LEGS intervention as standard of care in clinical PAD pathways if 60% of the components were delivered as intended within 15 days of follow-up, whilst accepting a 10% margin of error. A total of 93 patients had to complete the follow-up in order to report this within a 95% confidence interval with 90% power.

Analyses were performed using SPSS version 24.0 and R software. A pre-drawn statistical analysis plan was formulated and included in the study protocol. Data are presented as mean with standard deviation (SD) or absolute values with proportions. Normality of distributions was assessed using the Kolmogorov-Smirnov test and the degree of skewness and kurtosis of each variable of interest. Comparisons were performed using either the t-test, Mann-Whitney U or Wilcoxon Test, or Fisher’s exact test for comparisons between two groups, based on the nature of the data compared. For comparisons across groups, Analysis of Variance (ANOVA) was used. A p value <0.05 was considered statistically significant. Data was maintained and analysed by the NIHR Leicester Biomedical Research Centre (BRC), independent to investigators.

Baseline characteristics

Overall, 120 participants (40 female, 33%) took part. Table 1 describes baseline characteristics (upon referral to secondary care specialist vascular services). Of interest, 89 patients (74%) presented with CLTI (19 with tissue loss, 16%). Overall, 40 (33%) were inpatients at baseline and 80 (67%) were seen in a clinic. One was seen in clinic and admitted to the ward on the same day (to undergo a major amputation due to fulminant sepsis; Rutherford stage 6). Table 2 describes the types of vascular procedures/interventions that 84 patients underwent after their index appointment. All claudicants were initially treated with conservative means. Overall, 129 patients were approached to take part, of which 120 consented (93% intervention recruitment rate). A total of 118 (98% intervention retention rate) completed six-month follow-up i.e. their care was provided based on the LEGS intervention for at least six months. The mean intervention fidelity score at baseline (i.e. day of the clinic appointment or day of discharge for inpatients - primary outcome measure) was 63% [95% Confidence Interval (CI): 39-68%, SD: 5%]. Table 3 describes the intervention fidelity scores at baseline, 30 days, and six months (end of prospective follow-up) for inpatients and outpatients. At 15 days after taking part in the study, the GPs of 108 patients (90%) had received the LEGS intervention GP leaflets and letters and 119 patients (99%) had received the LEGS education document. Of these, 81 (68%) had read and understood the document; only four asked for a translated version (3%). Of the 81 who read the LEGS leaflet, 66 (81%) needed help from carers or healthcare staff and/or had queries. During six months of follow-up, eight patients (6.7%) died (all cardiovascular deaths), four (3.3%) had a major lower limb amputation, 12 (10%) had a major cardiovascular event other than re-admission for a lower-limb pathology, 12 (10%) were admitted due to CLTI, one (1%) was re-admitted due to acute lower limb ischaemia and underwent a surgical embolectomy (previous superficial femoral artery angioplasty), and 12 (10%) underwent re-intervention. Overall, 43 (36%) saw their GP at least once after they took part in the study, and 22 (18%) had at least one community care appointment. Table 4 describes pharmacotherapy prescribed before the patients took part in the study, at baseline, and follow-up. More patients were prescribed an antiplatelet, statin, an anticoagulant, and blood pressure medications at six months compared to baseline.

Table 5 and Table 6 describe secondary outcome measures of interest, including quality of life in detail.

Limitations and next steps

This was a non-randomised prospective study aiming to assess intervention fidelity and feasibility of delivery. This is an essential step in the intervention development pathway set out by the Medical Research Council (MRC)¹¹. Given the non-randomised nature of the research, the cost-effectiveness of the LEGS intervention could not fully be assessed. Further, this research is not powered to examine differences in lipid levels or other surrogate markers of cardiovascular risk before and after the introduction of the LEGS checklist in the care of these patients - this was beyond the scope of the study. This research, however, has shown that the fidelity of the LEGS intervention, especially during the initial period after patients present to secondary care, is acceptable and LEGS can be easily introduced in the routine care of patients with PAD who present with severe IC or CLTI. It has also identified areas on which clinicians will have to focus before further research and when implementing the LEGS intervention (should they wish to do so). The next step before adopting the intervention internationally as essential standard of care is to assess its cost-effectiveness, based on established guidance on complex interventions¹¹. At the same time, all medical targets and constituents of the LEGS intervention are based on level 1A randomised evidence (e.g. treatment for hypertension and hyperlipidaemia) and widely accepted clinical guidelines^3,10. These individual treatment targets and algorithms have been tested in terms of clinical and cost-effectiveness in well-designed large international trials. The LEGS intervention brings together these well-established treatment targets in a streamlined manner, to help HCPs provide guideline-based care. As a result, the individual targets and treatment strategies used in LEGS do not require further assessment in randomised trials; this has already been performed. At the same time, the cost-effectiveness of LEGS is uncertain across different healthcare providers and countries. This must be proven before the intervention becomes a “mandatory” part of PAD care¹¹. In the meantime, LEGS is a safe, cheap, and easily implementable tool which can help clinicians provide streamlined BMT when treating patients with PAD. It is freely available and can be edited/customised for use within regions.