Trials / Not Yet Recruiting

Not Yet RecruitingNCT07498868

Detecting the Undetected: Heart Failure Screening at the Lymphoedema Point of Care

Detecting the Undetected: an Observational Cohort Study Evaluating the Health Economics, Clinical Utility, and Patient and Staff Experiences of Innovative Peptide Testing to Screen for Heart Failure in Lymphoedema Clinics

Status: Not Yet Recruiting
Phase: —
Study type: Observational
Enrollment: 618 (estimated)

Sponsor: Swansea Bay University Health Board · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

Heart failure affects more people than the four most common cancers combined. When identified early, management is more straightforward, preventing complications, hospitalisations, and fatalities. Breathlessness and fatigue are cardinal symptoms of heart failure that can present in a number of conditions. As a result, leg swelling, the third cardinal symptom, is the first noted in many people. The presence of leg swelling leads to patients being seen in lymphoedema clinics before the need for cardiology investigation has been identified. Lymphoedema is the presence of chronic oedema as a result of congenital abnormalities, inflammation, infection, trauma, or cancer and its treatments. The vast majority of lymphoedema patients have swelling in their legs. A recent study has shown that 9.4% lymphoedema patients need to be investigated for heart failure. At present, the need for investigation is identified by performing a laboratory blood test, which takes time to arrange and complete. An alternate point of care test can provide a result in 12-minutes at the lymphoedema appointment, and enable appropriate action to be taken. This can reduce the demands on primary care and shorten the chain of events to a specialist assessment, as well as reducing inappropriate referrals. This research, funded by NHS Wales Performance and Improvement, will perform a point of care test to screen for possible heart failure in lymphoedema clinics and establish the clinical utility by exploring the experiences of patients and staff involved and determining the health economic benefits. A supplementary aim is to compare the point of care test to the currently used laboratory test in a subsample to promote confidence in the test and support efforts to spread and scale across all health boards in Wales on completion.

Detailed description

Globally, more than 26 million people (1-2% of the adult population) suffer from heart failure. In the UK, 1.4% of the population were diagnosed in 2014. It affects more people than the four most common cancers combined (lung, breast, bowel, prostate). Early diagnosis and treatment are vital for preventing complications, hospitalisations, and death. The cardinal symptoms are breathlessness, peripheral swelling/oedema, and fatigue. Oedema in the legs and lungs are key symptoms and most patients fall on a spectrum ranging between the two. Leg oedema occurs when the lymphatic system is unable to remove fluid, leading to an accumulation in the lower body. This increased fluid causes the release of proteins called brain natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP). These proteins force the body to try and maintain blood pressure and in people with heart failure, this leads to leg oedema. When oedema is present for 3-months or longer it has become chronic and is diagnosed as lymphoedema. Primary lymphoedema occurs as a result of congenital abnormalities and secondary lymphoedema occurs following inflammation, infection, trauma, cancer, or cancer-related surgeries and treatments. Most patients with heart failure do not have any symptoms and when leg oedema is noticed, they may be seen in lymphoedema clinics before heart failure is considered as a possible cause. This provides an opportunity to screen for undetected heart failure and is important to ensure the right treatment and onward referrals to optimise patient management. However, at present this is not done and the burden of heart failure screening falls on primary care. Due to the potential for heart failure to present without any symptoms, 79% of patients are diagnosed following a hospital admission and National Institute for Health and Care Excellence (NICE) guidelines are not being met due to the demand placed on primary care. As well as the impact on patient care and mortality, the financial consequence to the NHS of an in-hospital diagnosis is an additional £2,485 per patient. There is a current UK-wide need to support screening, access to specialist assessment, and timely management. The availability of point of care testing can support the early detection of heart failure but feasibility and clinical utility in lymphoedema clinics where a large number of undiagnosed heart failure patients may attend has not been explored. The cost per test is extremely low (£43 including clinician time) compared to the cost of diagnosing heart failure on admission to hospital (£2,485). Early identification can provide significant economic benefits to the NHS by reducing admissions at crisis and more importantly, transforming and streamlining existing pathways. Testing of NT-proBNP is recommended by the European Society of Cardiology due to its high negative predictive value that can exclude heart failure, enabling a reduction in unnecessary appointments or investigations. The lower level of normal is 125 ng/L and the National Institute for Health and Care Excellence (NICE) identifies a threshold of 400 ng/L, below which heart failure is unlikely. Patients with an NT-proBNP level between 400 and 2,000 ng/L should be referred to a specialist and receive an echocardiogram within 6-weeks, and those above 2,000 ng/L should be seen within 2-weeks. At present, a patient with suspected heart failure presenting to a lymphoedema clinic must go through 12 steps including two in-person appointments before they attend an appointment with a cardiologist. Current timescales in Wales vary and can range from 4-weeks to 18-months, during which the condition could worsen, asymptomatic patients could become symptomatic, or emergency admissions and fatalities could occur. Indeed, historical data from one health board in Wales shows that delayed NT-proBNP testing increased acute hospital admissions, bed days, and mortality. In addition, while screening has improved in primary care, 20% of patients with an NT-proBNP greater than 2,000 ng/L and 10% with an NT-proBNP between 400 and 2,000 ng/L are not referred for further investigation in line with NICE guidance, demonstrating a limitation in current pathways. Delays in screening are confounded by inappropriate referrals, which are as high as 34% in local health boards across Wales. Recent, unpublished, pilot work in winter 2024 found that of 30 lymphoedema patients undergoing laboratory-based NT-proBNP testing, 50% required further cardiology investigation. Furthermore, 213 lymphoedema patients unknown to cardiology were tested for heart failure and 21 (9.86%) were subsequently diagnosed, enabling their pathway to be optimised. Providing lymphoedema clinics with the resources to perform point of care NT-proBNP testing can reduce the number of steps required to see a cardiologist, enabling more timely access to appropriate care. This eliminates two in-person appointments and considerably reduces the time to a specialist appointment and further investigation. Obtaining a rapid NT-proBNP test result can optimise patient management and reduce NHS demands, patient travel, and carbon emissions. The high negative predictive value of NT-proBNP testing can enable HF to be excluded, reducing HF waiting lists, unnecessary appointments, referrals, and the travel and carbon emissions associated with in-person appointments. As the first research exploring this innovative application of point of care testing, the patient and staff experiences, clinical utility, and health economic benefits of screening for heart failure in lymphoedema clinics are currently unknown. This data is important to evaluate the potential of making this business as usual and supporting a business case to spread and scale across Wales. This can lead to enhanced capabilities in lymphoedema clinics, streamlined processes, and proactive screening for a life-threatening condition in a timely manner. This research aims to test the hypothesis that point-of-care N-terminal prohormone of brain natriuretic peptide (NT-proBNP) testing improves the detection and onward referral of lymphoedema patients with undetected heart failure, reduces harm, financial waste, and improves patient outcomes. A clinical audit has been completed to establish current practice and will be used as a baseline against which the findings of this study will be compared. Discussions with colleagues across Swansea Bay University Health Board from lymphoedema, cardiology, point of care testing, and laboratory medicine informed the study design so that there is minimal impact on clinical care, preventing overburdening of staff and waiting lists. Patients attending lymphoedema outpatient appointments in Swansea Bay University Health Board over a period of 18-months will be invited to participate, until saturation, with a target sample size of 618. The sample size has been calculated based on published data reporting that 9.38% of bilateral leg lymphoedema patients have an NT-proBNP level greater than 400 ng/L. To identify this prevalence with 95% confidence and a precision of 2.3%, a sample size of 618 is needed. Further, for the method comparison phase of the study, 100 participants will be included. This sample size has been calculated based on previous work showing a 35.6% difference in NT-proBNP test results from 2 different devices, albeit not those that will be used in this study. To observe the same difference at an alpha level of p ≤ 0.05 with 80% power, a sample size of 22 is needed. With the aim of observing a smaller difference, a sample size of 100 has been selected for this element of this study. There are two phases to the study, as described in the protocol: 1) method comparison; 2) detecting the undetected. In the description below, the phases will be described in reflection of the recruitment and consenting process which has three elements: 1) screening; 2) clinical research appointment; 3) interviews. Each element relates to a different visit/attendance. The staff focus groups will be described separately in this section. Element 1 - Screening For the duration of the study, until recruitment is complete, the clinical team will ask patients if they would like to be contacted by the research team. The contact details of those that would like to be contacted will be passed on to the research team who will telephone the patient to explain the research opportunity and determine eligibility. The Screening Participant Information Sheet will be sent (by email or post) to those interested and they will be given until their next lymphoedema appointment to consider their participation. The Recruitment Leaflet will be placed in the waiting room and shared on social media to further support recruitment and awareness of the research. The Recruitment Leaflet contains an overview of the study and information on who to contact to request more information or a copy of the participant information sheets. A leaflet design was preferred after being reviewed by members of the public and lymphoedema patients involved in our engagement activities during the design of the study. In current clinical practice, 14 days prior to the lymphoedema appointment, all patients are sent an electronic link (email or sms) to complete the lymphoedema patient reported outcome measures (LYMPROM) questionnaire which is used clinically as part of their assessment. For patients consenting to participate in this study, LYMPROM data will be anonymised and included in the study. This is explained in the Screening Participant Information Sheet. On attending their lymphoedema appointment, patients will be reminded of the opportunity to participate in the research by the clinical team and given a copy of the Screening Participant Information Booklet if they have not already requested this prior to attending. They will be given time to read it and ask a member of the research team any questions. When the patient makes a decision on participation, consent will be taken by a member of the research team after checking that the patient has understood the research and the risks and benefits to them, and answering any questions they may have. Some participants may prefer to take the information away and participate at their next appointment and it will be made clear to them that this is an option. After taking consent, a lancet will be used to take a 20 µL fingerprick blood sample which will be tested on the Roche Diagnostics LumiraDx point of care testing device. A test result will be provided in 12-minutes which will determine the participant's next step in the study. The participant will be told the test result and what this means for their health and involvement in the study. The different possibilities are explained in the three paragraphs below: 1. If the NT-proBNP level is less than 400 ng/L, Their involvement will end (unless attending a future interview), a Patient Experience Interview Participant Information Sheet will be provided for consideration, and the participant will be free to leave. If they wish to be involved in an interview, contact details are provided on the information sheet and it is up to the participant to contact the research team. 2. If the NT-proBNP level is greater than or equal to 2,000 ng/L, Involvement in the study will end, no further tests will be performed, and the participant will be urgently referred to cardiology services, receiving an appointment confirmation when the referral has been processed by Swansea Bay University Health Board Cardiology Service. 3. If the NT-proBNP level is between 400 and 1,999 ng/L (inclusive) The participant will need to attend a clinical research appointment at another date, time, and location within Swansea Bay University Health Board. The referral will be made and the participant will be given Clinical Research Appointment and Patient Experience Interview Participant Information Sheets to review in their own time, containing the contact details of the research team for them to ask any questions and express an interest in participating in an interview. Participants referred for a clinical research appointment will receive an appointment confirmation from Swansea Bay University Health Board Cardiology Service when the referral has been processed. To support the clinical research appointment, all participants referred to this element of the study will be asked to provide a 4mL venous blood sample for testing their full blood count, and a 5 mL venous blood sample for testing their urea and electrolytes. These samples will be sent to the laboratory for testing as in routine clinical practice, and the results will be recorded on the patient's record so they can be reviewed by the cardiologist in the clinical research appointment. After providing the venous samples, the participant will be free to leave. An exception to participants being free to leave after the point of care test is when a participant has consented to participate in the method comparison phase of the study. A maximum of 100 participants will be included in this phase. For these participants, a 5 mL venous sample will be taken from their arm by a trained and experience phlebotomist before they leave the lymphoedema clinic. The sample will be sent to the laboratory for testing as in routine clinical practice. As will be the case throughout the study, participants can withdraw from the method comparison phase if they have changed their mind after originally giving consent and they will be reminded of this. In current clinical practice, after attending a lymphoedema appointment, all patients are sent a digital link (email or sms) to complete the lymphoedema patient reported experience measures (LYMPREM) questionnaire which is used to evaluate the care received. For consenting participants, this data will be anonymously included in the study as a measure of patient experience. This is explained in the Screening Participant Information Sheet. To support health economics analyses to quantify the benefit of performing the NT-proBNP test at the point of care, the number of laboratory tests each participant has had in the 12-months before and after their involvement in the study will be captured from their clinical record and compared. This is explained in the Screening Participant Information Sheet. Element 2 - Clinical research appointment Participants will attend a clinical research appointment led by a Consultant Cardiologist and supported by an Advanced Lymphoedema Practitioner. A member of the research team will also be present and the participant will have the opportunity to ask any questions before their understanding is confirmed and written informed consent taken. The participant will undergo an electrocardiogram and echocardiogram and the cardiologist will review the findings along with the already provided full blood count and urea and electrolytes blood test results. An outcome will be determined and the patient will be informed by the cardiologist before they leave the appointment. The consequences and next steps will be explained to them and clinical care will continue as determined. All patients diagnosed with heart failure will be asked to complete the Kansas City Cardiomyopathy Questionnaire at the end of their appointment and this will be completed again over the telephone after 6-months to support clinical utility and health economics analyses. After having the opportunity to ask any questions to the clinicians and researcher, patients will be reminded of the patient experience interviews and how to be involved. They will then be free to leave and their involvement in the study will end, unless they participate in an interview. Element 3 - Semi structured interviews The Patient Experience Interview Participant Information Sheet will be given to all participants, apart from those urgently referred for a cardiology appointment (i.e. NT-proBNP \> 2,000 ng/L) after their lymphoedema appointment, giving them time to read and consider their involvement in their own time. Participants who attend a clinical research appointment will also be reminded verbally of the interview opportunity. All interviews will take place online on Microsoft Teams with a member of the research team at a time convenient to the participant. Three groups of interest will be included in interviews: 1) those with a point of care NT-proBNP test level less than 400 ng/L; 2) those with a point of care NT-proBNP test level between 400 and 1,999 ng/L who were diagnosed with heart failure; 3) those with a point of care NT-proBNP test level between 400 and 1,999 ng/L who were not diagnosed with heart failure. When the participant joins the online meeting, the opportunity to ask any questions will be provided and verbal consent will be confirmed. If the participant does not consent, the interview will not continue and no recording will be made. The researcher will ensure that cameras are turned off and no video footage is being displayed before setting the interview to record. A 1-hour semi-structured interview will be completed, using an interview template. At the end of the interview, the recording will be stopped, the participant will be thanked for their time, their involvement in the study will end, and their care will continue as normal. The researcher may make paper notes during the interview and these will be anonymously typed up electronically as soon as possible after completing the interview. The recording will be anonymously transcribed into an electronic format by a member of the research team as soon as possible after the interview has ended, and the recording will be permanently deleted. Staff focus groups All lymphoedema clinical staff involved in the research will be invited to participate in a focus group led by a member of the research team. The focus group will be 1-hour long, in-person, and include up to 4 members of staff. The focus group will be recorded using a recording device so that it can be anonymously transcribed by a member of the research team as soon as possible afterwards, and the recording will be permanently deleted. Paper notes may be made during the focus group and these will be typed up electronically as soon as possible and the original destroyed. Staff will sit in a welcoming environment and be able to share their experiences of the point of care test. The researcher will initiate the discussion with open questions and will let participants express themselves and interact with one another. The researcher will remain out of discussions to prevent leading the conversation but will encourage participants when a topic of interest is raised and more details would support the analysis. At the end of the focus group, participants' involvement in the study will end and they will be free to leave. The research steering group including the research team, clinicians, patient representatives, Welsh Government, Roche Diagnostics, research governance, and data protection representatives will meet quarterly throughout the duration of the research to provide oversight, address any issues arising, discuss the results, and advise on dissemination. These meetings will include reviews of recruitment to ensure that sample sizes are achieved within the duration of the study.

Conditions

Timeline

Start date: 2026-05-01
Primary completion: 2027-10-01
Completion: 2028-09-01
First posted: 2026-03-27
Last updated: 2026-03-27

Locations

1 site across 1 country: United Kingdom

Source: ClinicalTrials.gov record NCT07498868. Inclusion in this directory is not an endorsement.