Can a Dedicated Chronic Limb-threatening Ischaemia (CLTI) Clinic Improve Patient Self
Conditions: Chronic Limb Threatening Ischemia
Sponsor: The Leeds Teaching Hospitals NHS Trust

 
 
 
Study Protocol 
 
 
Can a dedicated chronic limb-threatening ischaemia (CLTI) clinic improve patient 
self-reported quality of life? 
 
 
Protocol v 1.6 
 
 
 
 
 
 
Date: 14/11/2022  
This protocol has regard for the HRA guidance.  
 
 
1. Background 
 
Chronic limb-threatening ischaemia (CLTI) is the most severe form of peripheral 
arterial disease (PAD). It affects 1% of the population and its incidence is expected 
to rise. It is a condition where the circulation to one, or both limbs is inadequate. It 
requires investigation and may require surgery in order to improve the blood flow to 
the affected limb(s). Without improvement in circulation, ulcers and gangrene set in, 
and the only cure is a major limb amputation. 
 
Vascular surgery units in the United Kingdom have undergone centralisation into 
regional networks over the last decade in order to consolidate vascular surgery into 
‘high volume centres’ to provide high quality care and better outcomes for patients.  
 
However, national analysis of the performance of units has demonstrated that only 
50% of CLTI patients are revascularised within the ‘deliberately-challenging timeline’ 
issued by the Vascular Society of Great Britain and Ireland (Birmpili et al., 2021; 
Vascular Society of Great Britain and Ireland, 2019).  
CLTI already comprises more than 50% of vascular unit workload and the 
prevalence of CLTI is expected to rise, further increasing the burden on vascular 
services (Fowkes et al., 2016; Vascular Society of Great Britain and Ireland, 2018, 
2021).  
 
There is ample evidence demonstrating a strong inverse correlation between the 
provision of specialist outpatient clinics in the assessment and management of 
diabetic foot ulcers and major lower limb amputation (Joret et al., 2019; M Kerr, 
Rayman, & Jeffcoate, 2014; Marion Kerr, 2017; Monteiro-soares, Vale-lima, 
Martiniano, Dias, & Boyko, 2021; Paisey et al., 2017), Diabetic foot ulceration is a 
condition which has significant overlap with CLTI. It could therefore be inferred that a 
similar service for CLTI patients would also confer the same benefits. 
 
As many as 50% of CLTI patients also suffer from a significant degree of frailty, 
which makes treating patients with the condition more perilous  (Houghton et al., 
2021). The current guidance from the Vascular Society of Great Britain and Ireland 
recommends that patients who suffer with frailty should have access to elderly 
medicine specialists who can help with optimisation, complex decision making or 
advanced care planning. There is growing evidence that these services have 

tangible benefits for vascular patients (Gordon, Evans, & Dhesi, 2017; J. Partridge, 
Sbai, & Dhesi, 2018; J S L Partridge et al., 2017; Judith S L Partridge et al., 2015) 
 
At the Leeds Vascular Institute, we have implemented a dedicated CLTI clinic to 
assess and manage patients with the condition. Whilst there is limited evidence that 
these rapid access clinics can facilitate review and management of the condition, 
thereby successfully preventing major amputation in CLTI patients, the results are 
typically from single centre data series (Khan et al., 2020; Nickinson et al., 2021). 
There is a paucity of evidence evaluating patient opinions of this type of service and 
non that demonstrate any impact on their quality of life.  
 
Furthermore, we have integrated an elderly medicine service [Perioperative Medicine 
for the Older Person undergoing Surgery (POPS)] to facilitate clinic reviews, decision 
making, advanced care planning for elderly (aged > 65 years old), medically complex 
(1 or more seriously debilitating medical conditions) and/or frail (Rockwood Clinical 
Frailty Score > 5) vascular patients. The elderly medicine service exists as a 
separate entity from the CLTI clinic and sees vascular patients with any vascular 
pathology, including aneurysmal or carotid disease in addition to CLTI. However, a 
significant proportion of patients seen in the POPS clinic originate from the CLTI 
clinic. Our area of interest with this is specifically CLTI as evidence suggests that 
frailty is more prevalent amongst this cohort than aneurysmal patients.  
 
 
 
2. Rationale. 
 
As previously mentioned, there is good evidence to suggest that specialist outpatient 
clinics are associated with good limb salvage outcomes, both for diabetic and CLTI 
patients.  
All of the evidence that supports the use of CLTI clinics has been focused on clinical 
outcomes, but to our knowledge, there is no study that exists which has evaluated 
the benefit of the service on patient self-reported quality of life.  
 
Additionally, elderly and/or frail CLTI patients are referred into the POPS clinic to 
help with complex decision making and advanced care planning. 
 
These services have been designed and implemented with patients in mind but there 
is no evidence which actually determines the impact of these services from the 
patient’s perspective. 
 
Patient reported outcomes are an important measurement of a quality service and it 
is seldom reported in surgery. There is some limited evidence to suggest that CLTI 
clinics will be favourably reviewed by patients (Khan et al., 2020), but no evidence at 
all to determine if they can improve quality of life.  
 
3. Theoretical Framework 
 
The aim with CLTI treatment is to achieve limb salvage, that is to prevent the leg 
from deteriorating to the point of necessitating amputation. Limb salvage is seen as 
the ultimate goal following CLTI intervention.  

The assumption is that patients who have their leg successfully saved, and avoid 
amputation will have a better quality of life because of it. However this has not been 
formally identified.  
The POPS service exists to improve care provided to the most complex and frail 
CLTI patients. An evaluation of the service in terms of its clinical impact is already 
underway, but again we lack any patient feedback on the service. 
 
 
4. Research Question / Aim 
 
4.1 Objectives 
 
To evaluate the difference that CLTI clinic attendance and management has on 
patient-reported quality of life.  
Additionally, we want to explore what CLTI patients referred into the POPS service 
feel about the service they have received, if it has been beneficial, helped them 
make complex decisions or provided more information on their condition.  
 
 
4.2 Outcome 
 
We hypothesise that patients will have a statistically significant improvement in self-
reported quality life after CLTI clinic assessment management in comparison to 
before CLTI clinic assessment and management. 
We propose that the POPS service will be favourably reviewed by patients when 
provided with a structured questionnaire. 
 
5. Study Design and Methods of Data Collection and Data Analysis 
 
This will be a prospective observational repeated measures study.  
Patients who are referred into the CLTI clinic will be identified from the clinic register, 
which also distinguishes between new patients and patients who are being followed-
up. 
New patients who are attending the CLTI clinic will be approached to enrol into the 
study. Patients who consent to enrolment in the study will have their details recorded 
on a register which will enable the researchers to identify when the next 
appointments are due and can therefore determine when the next questionnaire can 
be delivered.  
 
If patients consent to participate, they will be asked to complete: 
- 
Their first EuroQol-5D questionnaire immediately prior to their first CLTI clinic 
appointment 
- 
1 feedback survey about their CLTI clinic experience after their first appointment 
- 
A second EuroQol-5D questionnaire 6-12 weeks after their treatment is complete 
- 
A third EuroQol-5D questionnaire at 12 months after the initial appointment 
 
Separately, patients who are then referred from CLTI clinics to the POPS service at 
(based on the POPS referral criteria) will be asked if they wish to answer a 
structured questionnaire about the POPS service. If they agree, they will be asked to 
complete: 

- 
1 additional feedback survey about their POPS clinic experience immediately 
after their appointment 
 
This is in addition to the 4 questionnaires and surveys they have completed / will be 
asked to complete as part of the CLTI clinic evaluation. 
 
The anticipated study start date is 1st December 2022, with primary completion 
expected around 1st July 2023. The expected study completion date is 1st July 2024.  
  
 
5.1 Data collection 
 
Data will be collected using the standardised EuroQol-5D questionnaire. This is a 
validated patient reported outcome measure which has been widely used in studies 
evaluating self-reported quality of life. 
 
A license to use the questionnaire has been authorised and granted. The EuroQol 
survey will be delivered electronically using LimeSurvey software. It can be 
completed by study participants, with or without promptin from their carers or 
relatives, or researchers on behalf of study participants.  
 
Additionally a structured questionnaire evaluating the CLTI clinic and/or POPS 
service using a Likert scale and free text comments will be administered to 
participants. We plan to use an iPad or tablet to administer the surveys to patients.  
 
Survey responses that are entered are stored electronically within LimeSurvey, both 
on an app and also on a website cache. The survey itself contains no identifiable 
information at all.  
 
Identifiable data will only be kept on a study registry within a password protected 
cloud drive attached to an NHS.net account. NHS.net is Caldicott compliant and 
therefore adequate for handling patient identifiable data. The purpose of this registry 
to is to ensure that subsequent survey responses from the same patients are linked 
together (as it is a repeated measures design) and also to highlight when new 
appointments are due. This information is not contained within the EuroQol survey.  
 
6. Study Setting 
 
The study will take place in the outpatient suite waiting room. Patients who are 
attending their first CLTI appointment and have consented to participate will be given 
the questionnaires on a tablet computer to complete. Identifying patients from the 
clinic register targets the exact demographic cohort. It is a single centre study. The 
POPS service is also in an outpatient suite.  
 
7. Sample and Recruitment 
 
7.1.1 Inclusion Criteria 
 
All CLTI patients seen and enrolled in the CLTI clinic are eligible.  
 

7.1.2 Exclusion Criteria 
 
Patients who have significant cognitive impairment and are unable to communicate 
will be excluded, as they will be unable to respond to the questions. Patients with 
mild cognitive impairment but still demonstrate capacity that may require prompting 
from carers or relatives in order to answer questions can still be included as the 
EuroQol-5D is validated for this purpose.  
 
7.2 Sampling 
 
We will adopt a convenience sampling strategy. The rationale for this strategy is the 
available pool of respondents who attend the CLTI clinic. We have chosen a sample 
size of between 50 – 100 patients. The CLTI clinic runs 3 times weekly and attempts 
to see 3-4 new patients per clinic, which means on average 9 – 12 patients per 
week. This would mean we should achieve our sample in around 10 weeks. 
However, pragmatically speaking, not every clinic will have the same number of new 
patients, not every patient will be suitable and some patients will be lost to follow-up. 
Hence we have a range of between 50 – 100 responses would be sufficient.  
 
There is no set amount of structured feedback questionnaire responses required, 
either of the CLTI or POPS clinic. 
 
 
7.3 Sample identification 
 
The researchers will identify the participants from a list of patients due to attend CLTI 
clinic, by attending the clinic and receiving a copy of the appointment schedule.  
The research team consist of those who provide clinical care to those patients in 
clinic, and therefore have access to identifiable data as part of their routine clinical 
role. Patients who have been referred to the POPS clinic from the CLTI clinic and 
consented to participate will be known to the researchers directly 
 
 7.4 Consent 
 
Consent will be obtained in clinic, prior to the patient’s first appointment. One of the 
research team will approach the patient, explain the nature of the study and provide 
them with a patient information leaflet. 
There will be the opportunity to ask questions prior to consenting.  
Patients who have mild cognitive impairment can still be included if they demonstrate 
capacity and consent to enrolment, even if they require some guidance in answering. 
The EuroQol-5D survey can be administered to someone else on behalf of the 
intended study participant who can prompt the participant to respond. 
 
8. Ethical and Regulatory Considerations 
 
8.1 Assessment and management of risk 
 
There won’t be any additional risks or harm to patients as a result of participation in 
the study because they are only required to fill out questionnaires. If patients become 
distressed during the provision of routine care, they can raise their issues with the 

researchers who are also care providers, or any of the care providers in the CLTI 
clinic. Our CLTI Vascular Nurse Specialist overseas patients seen in the clinic and  
acts as a point of contact for patients who have questions or issues during their 
treatment, whether that is attending appointments, or lack of communication or pain. 
Patients are given a card with her direct number (0113 392 0943) and can get in 
contact during office hours (Mon-Fri 0800-1700). If concerns can’t be addressed at 
this level, patients will be signposted to the Patient Experience team (PALS) on 0113 
206 6261 or patientexperience.leedsth@nhs.net.  Any safeguarding issues that are 
incidentally identified during the study will be communicated to the patient’s GP or 
the adult safeguarding team. 
 
An REC opinion will be sought and a draft IRAS form has been written in the 
anticipation of submitting it. The study will not begin until the relevant REC has 
reviewed and approved the proposal.  
 
Amendments to the study will require a valid notice of amendment to the REC for 
consideration. This will be discussed with the Chief Investigator first. 
 
8.2 Patient and Public Involvement 
 
A PPI initiative was undertaken at LGI with a focus on CLTI. Patients were consulted 
with their carers about the condition as a whole. The main findings were that the 
condition as a whole was generally not well understood by patients and any future 
initiatives that involve patients and/or relatives in redesigning the service would be 
welcome. 
8.3 Protocol Compliance 
 
Any protocol deviations that occur will be reported to the Chief Investigator  
 
8.4 Data Protection and Patient Confidentiality 
 
Personal information which could identify patients will be kept secure on a password 
secured registry contained on an NHS.net secure cloud drive. NHS.net is Caldicott 
compliant and is appropriate for handling sensitive data. The purpose of this is solely 
to identify patient appointments which allow for linking study responses as per the 
repeated measures study design.  
 
The EuroQol-5D survey has no patient identifiable data at all, and the responses are 
stored on the LimeSurvey application. 
 
The principal investigator will have access to the registry of patients with identifiable 
data. This will only be available to the Principal Investigator and Chief Investigator.  
Analysis can be performed by other members of the research team as it doesn’t 
require any handling of sensitive data. Data will be stored for 5 years 
 
8.5 Indemnity 
 
Insurance is not required above and beyond the NHS indemnity scheme because 
the research will only be conducted on NHS sites at the time of other clinical (ie 
outpatient appointments). 

 
Access to the Final Study Dataset 
 
The Principal Investigator and Chief Investigators will have access to the final 
dataset. 
 
9. Dissemination Policy 
 
The data will be owned by the Chief Investigator and the Trust. On completion, a 
Final Study Report will be prepared. The intent of the investigators will be to 
disseminate this information at scientific meetings and for publication. Participants 
can contact the Principal Investigator regarding the results once the Final Study 
Report has been written or when the study has been published. 
 
Authorship Eligibility 
 
The chief investigator, principal investigator and other researchers who participate in 
data collection, extraction, analysis and write-up will be considered for authorship. 
 
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