A feasibility study to inform the design of a randomised controlled trial to identify the most clinically effective and cost-effective length of Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT).

BACKGROUND: Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin (LMWH). Current data recommend LMWH for anticoagulation as far as 6 months, yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. OBJECTIVES: (1) To identify the most clinically and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis (CAT); (2) to identify practicalities of conducting a full randomised controlled trial (RCT) with regard to recruitment, retention and outcome measurement; and (3) to explore the barriers for progressing to a full RCT. DESIGN: The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT) trial is a randomised, multicentre, feasibility mixed-methods study with three components: (1) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months' treatment (current licensed practice) in patients with locally advanced or metastatic cancer, consulted in three clinical settings (haematology outpatients, oncology outpatients and primary care); (2) a nested qualitative study, including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT, and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study, and potential barriers and concerns to participation; and (3) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care. SETTING: A haematology outpatients department, an oncology outpatients department and primary care. PARTICIPANTS: Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT. INTERVENTIONS: Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months' treatment in patients with locally advanced or metastatic cancer. MAIN OUTCOME MEASURES: (i) The number of eligible patients over 12 months; (ii) the number of recruited patients over 12 months (target recruitment rate of 30% of eligible patients); and (iii) the proportion of randomised participants with recurrent venous thromboembolisms (VTEs) during follow-up. RESULTS: Following several delays in setting up the RCT component of the study, 5 out of 32 eligible patients consented to be randomised to the RCT suggesting progression to a full RCT was not feasible. Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation, and a fear of randomisation to their non-preferred option. Views were largely influenced by patients' initial experience of CAT. Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence. Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination, with no consensus on which specialty should best manage such cases. CONCLUSIONS: The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres. However, it is unlikely that these other sites would have access to more eligible patients. The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge. As it is unlikely that a prospective study will successfully recruit, other strategies to accrue relevant data are necessary. Currently the LONGHEVA (Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism) registry is in development to prospectively evaluate this important and common clinical scenario. STUDY REGISTRATION: This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976. FUNDING DETAILS: Funding for the ALICAT trial was provided by the Health Technology Assessment programme (10/145/01) in response to a themed funding call. The study was designed in accordance with the initial funding brief and feedback from the review process.

A feasibility study to inform the design of a randomized controlled trial to identify the most clinically and cost effective anticoagulation length with low molecular weight heparin in the treatment of cancer associated thrombosis (ALICAT): study protocol for a mixed-methods study.

BACKGROUND: Venous thromboembolism is common in patients with cancer and requires anticoagulation with low molecular weight heparin. Current data informs anticoagulation as far as six months, yet guidelines recommend anticoagulation beyond six months in patients who have locally advanced or metastatic cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. ALICAT (Anticoagulation Length in Cancer Associated Thrombosis) is a feasibility study to identify the most clinically and cost effective length of anticoagulation with low molecular weight heparin in the treatment of cancer associated thrombosis. METHODS/DESIGN: ALICAT is a randomized multi-centre phase two mixed-methods study with three components: a randomized controlled trial, embedded qualitative study and a survey investigating pathways of care. The randomized controlled trial will compare ongoing low molecular weight heparin treatment for cancer-associated thrombosis versus cessation of low molecular weight heparin at six months treatment (current licensed practice) in patients with locally advanced or metastatic cancer. The embedded qualitative study will include focus groups with clinicians to investigate attitudes to recruiting to the study, identify the challenges of progressing to a full randomized controlled trial, and also semi-structured interviews with patients and relatives/carers to explore their attitudes towards participating in the study and potential barriers and concerns to participation. Finally, a UK wide survey exercise will be undertaken to develop a classification and enumeration system for the cancer associated thrombosis models and pathways of care. DISCUSSION: There is a lack of evidence determining the length of anticoagulation for patients with cancer associated thrombosis and subsequently treatment length varies. The ALICAT study will consider the feasibility of recruiting patients to a phase three trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37913976.