Title: Hospital Deep Vein Thrombosis Detection Study in Cancer Patients Receiving Palliative Care (HIDDEN 2)
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Venous thromboembolism (VTE) is the commonest preventable cause of hospital associated harm and mortality, with 60% of all VTEs occurring within 90 days of hospital admission. Compared to the wider population, patients requiring acute medical hospitalisation have a 20% increased risk of VTE due to the acute medical illness itself and concurrent immobility. Cancer patients are at even greater risk of VTE as they already have a high background thrombotic risk due to the local release of cancer procoagulants and anticancer treatments such as chemotherapy, surgery and targeted therapies. The incidence of VTE increases with cancer stage and disease progression, those with advanced incurable cancer are at the greatest risk of VTE. The prevention of Hospital Acquired Thrombosis (HAT) is a priority for the Welsh Government, all hospitalised patients should be assessed for risk of HAT and receive Low Molecular Weight Heparin (LMWH) thromboprophylaxis in accordance with NICE Clinical Guideline 92. The clinical trials informing the NICE guideline for VTE prevention are over 20 years old and less than 15% of recruited patients had cancer. Furthermore, studies specifically excluded cancer patients receiving palliative care, although they are at particular risk of thrombosis and account for 80,000 UK admissions per annum. There has been considerable debate as to whether the current data can be applied to palliative care patients, with advanced cancer, since studies informing NICE guidance excluded patients of poor Performance Status (PS) or estimated prognosis less than 3 months. Furthermore, within a clinical environment where optimising quality of life is prioritised over life prolongation, the application of a daily injection as a safety measure to prevent early mortality may be less appropriate. The challenges of anticoagulants in the hospice setting have been well documented, including: associations with significant bleeding in up to 9% of inpatients and 7% of cancer patients as death approaches, raising safety concerns. The RfPPB-funded Hospice Deep Vein Thrombosis Detection study (HIDDen) (Ref: PB-PG-0614- 34007) identified a 28% prevalence of femoral DVT among cancer patients receiving palliative care at admission to a Specialist Palliative Care Unit (SPCU). There was minimal associated symptom burden and no survival difference between those with or without DVT. It also observed that 35% of screened patients had been admitted for end of life care, who would not be eligible for thromboprophylaxis. Whilst this data has already impacted on clinical hospice care, the UK hospice/SPCU population, represents a fraction of palliative care inpatients, with the majority (up to 80,000 per annum) admitted to the acute setting. It is believed these patients may often be of better PS and prognosis than those in HIDDen and the data not applicable to those admitted acutely to hospital. As a natural progression of HIDDen, which demonstrated feasibility to recruit from an often overlooked research population, the study needs to be repeated in the acute hospital setting, to best inform management strategies and hospital policy. In order to answer this important question, we plan to recruit 232 patients from four acute hospitals across South East Wales over 10 months. This will allow us to estimate the prevalence of DVT with a 95% confidence interval of no more than plus or minus 5 percentage points based on 17% prevalence and expected dropout of 5%.

Lay abstract: Patients with cancer are at a high risk of developing potentially dangerous blood clots (venous thromboembolism or VTE) due to the release of molecules which make the blood stickier. The risk of developing VTE is further increased by surgery, sudden medical illness and anticancer treatments such as chemotherapy, hormone therapy and immunotherapy. Most VTEs start as blood clots in the legs known as Deep Vein Thromboses (DVT) which may have no symptoms but classically present as swollen legs. Untreated, these DVTs can break off and lodge in the lungs forming Pulmonary Emboli (PEs), causing a breadth of symptoms including cough, shortness of breath, chest pain, collapse and sometimes death. Emergency hospital admission increases the risk of developing VTE by 20% regardless of whether a patient has cancer or not. Consequently, VTE prevention amongst hospitalised patients is an NHS health policy priority in England and Wales and has been shown to reduce avoidable harm and death. Cancer patients are seven times more likely to develop VTE than the general population and the risk is further increased in advanced cancer and by treatment of cancer with chemotherapy or immunotherapy. The studies upon which clinical guidelines for preventing VTE (thromboprophylaxis) are based, are over 20 years old and included less than 15% cancer patients. Also, studies excluded patients who were likely to have a poor outcome and who had a poor Performance Status (PS). It is therefore unclear whether we should apply these guidelines to patients with advanced cancer who are receiving palliative care. We recently published the Hospice Deep Vein Thrombosis Detection study (HIDDen) which looked at how many hospice patients were effected by VTE and how useful thromboprophylaxis would be for these patients. Leaving out 35% of patients who were admitted for end of life care, 28% of the remaining patients demonstrated large volume DVT. These caused few symptoms and there was no survival difference between those with or without DVT. Patients had high care needs and an average survival of 44 days. A Lancet Haematology Editorial concluded that thromboprophylaxis was of limited utility in hospice patients of poor PS and prognosis. These data have already changed the way we treat these patients. The UK hospice/Specialist Palliative Care Unit (SPCU) population, represents a fraction of palliative care inpatients - the majority (up to 80,000 per year) are admitted to hospital. Other data suggests the acutely admitted palliative patient is of better PS and prognosis and the data from HIDDen may not be applicable in the hospital setting. As a natural progression of HIDDen, we believe it is important that the study is repeated in the hospital setting, in a larger earlier-stage, better prognosis population. We propose a study in advanced cancer patients to find out: - How common DVT is in these patients when they come into hospital. - What symptoms these patients have. - The 90-day incidence of hospital acquired thrombosis. - If there is an association between DVT and survival. We plan to recruit 232 patients from four acute hospitals across South East Wales over 10 months, so that we may answer these important questions. By not undertaking this research we risk continuing to treat some of our most vulnerable poorly cancer patients according guidelines derived from out of date studies from an unrepresentative population.

Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: BLOOD;CANCER AND NEOPLASMS