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.


OBJECTIVE
(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.


METHODS
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.


METHODS
A haematology outpatients department, an oncology outpatients department and primary care.


METHODS
Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT.


METHODS
Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months' treatment in patients with locally advanced or metastatic cancer.


METHODS
(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.


BACKGROUND
This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976.
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.
Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.|Marie Curie Palliative Care Research Centre, Cardiff University, Cardiff, UK.
Simon I
SI
Noble
Marie Curie Palliative Care Research Centre, Cardiff University, Cardiff, UK.
Annmarie
A
Nelson
Department of Primary Care Clinical Sciences, University of Birmingham, Edgbaston, UK.
David
D
Fitzmaurice
South East Wales Trials Unit, Cardiff University, Cardiff, UK.
Marie-Jet
MJ
Bekkers
School of Healthcare Science, Cardiff University, Cardiff, UK.
Jessica
J
Baillie
Marie Curie Palliative Care Research Centre, Cardiff University, Cardiff, UK.
Stephanie
S
Sivell
Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
Joanna
J
Canham
Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
Joanna D
JD
Smith
Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
Angela
A
Casbard
Department of Surgery and Vascular Medicine, King's College Hospital, London, UK.
Ander
A
Cohen
Faculty of Health, Sport and Science, University of South Wales, Pontypridd, UK.
David
D
Cohen
Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, UK.
Jessica
J
Evans
Birmingham Primary Care Clinical Research and Trials Unit, University of Birmingham, Edgbaston, UK.
Kate
K
Fletcher
St Catherine's Hospice, Scarborough, UK.
Miriam
M
Johnson
Department of Academic Oncology, University of Hull, Hull, UK.
Anthony
A
Maraveyas
Marie Curie Palliative Care Research Centre, Cardiff University, Cardiff, UK.
Hayley
H
Prout
South East Wales Trials Unit, Cardiff University, Cardiff, UK.
Kerenza
K
Hood
D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D017144:Focus Groups; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000191:economics; D011446:Prospective Studies; D012107:Research Design; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000191:economics / Q000209:etiology; D016896:Treatment Outcome; D055815:Young Adult
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight