A Feasibility Study to Inform the Design of a Randomised Controlled Trial to Identify the Most Clinically and Cost Effective Length of Anticoagulation With Low Molecular Weight Heparin In the Treatment of Cancer Associated Thrombosis
Venous thromboembolism (VTE) is a term to describe blood clots in the legs known as a deep
vein thrombus (DVT) or lung, known as a pulmonary embolus (PE). It is a common condition,
which causes many symptoms including leg pain, swelling, chest pain and breathlessness. At
its most serious, VTE may lead to sudden collapse and death.
Treating VTE costs the UK National Health Service (NHS) £640 million every year, including
the long-term complications experienced by nearly a third of patients. VTE treatment usually
consists of three to six months blood thinning medicine known as an anticoagulant. For most
patients, a tablet called warfarin is used, which requires regular blood tests to ensure the
blood is adequately and safely thinned.
We also know that VTE is particularly common in cancer. In the UK, over 250,000 people are
diagnosed each year with cancer, of which nearly a fifth will develop VTE. Warfarin is a
potentially risky treatment in cancer patients because it may increase the risk of bleeding.
Also, VTE may come back in a fifth of patients who are treated with warfarin.
Research has shown that a medicine known as low molecular weight heparin (LMWH) is better
than warfarin at treating VTE in cancer patients and decreases the chance of VTE coming back
by half. LMWH is given as an injection once a day. Studies have shown that giving the drug
as an injection is acceptable to patients, as some patients prefer this to the regular blood
tests they need to have for warfarin monitoring. LMWH is also simpler to use since it does
not cause problems for patients taking other medicines which is a common problem for
patients taking warfarin.
Cancer patients get VTE because the cancer can make the blood sticky and this makes it more
likely to clot. It is recommended that patients take LMWH for six months only. However, if
someone still has a cancer after six months of treatment with LMWH, there is still a strong
chance that the VTE could come back because the cancer causing the blood clots has not gone
away. This means that these patients might benefit from taking LMWH for longer than six
months. We do not know though whether this would improve the patients' quality of life, help
prevent death, or be cost-effective to the NHS.
To help decide if continuing with LMWH would benefit patients, we need to compare the
effects of continuing with LMWH for an extra six months with the effects of not continuing
LMWH in a clinical trial. Because this has not been done before, the first thing we need to
do is see if it would be possible to carry out a full clinical trial with these patients. In
other words, will we be able to recruit enough patients, will LMWH be a good treatment for
them and will it be a reasonable cost?
To help answer these questions, we propose what is called a feasibility trial. This
feasibility trial will compare patients who continue to take LMWH for a further six months
with patients who do not continue to take LMWH. Patients with cancer, and who have been
taking LMWH for five months for VTE, will be recruited from oncology and haematology
outpatients departments and from GP practices.
Patients who are approached to take part in the study will be asked if they would be willing
to continue with LMWH for a further six months as part of a research study. If they say yes,
then they will be chosen at random to either receive the LMWH for a further six months
(intervention group), or to stop LMWH at six months, which is usual care (control group). We
will follow up patients for six months from recruitment and ask them to complete
questionnaires at three monthly intervals. These questionnaires will ask about their
symptoms and quality of life.
We will interview patients who do not wish to consent to the study to explore their reasons
why. We will also interview patients who do consent to the study, but who later withdraw
from the study to explore their experiences and reasons for withdrawal. We will also explore
the views of clinicians towards continuation of LMWH and how they feel about the trial.
Focus groups will be held with two groups of clinicians from each care setting. By
collecting this information, we will be able to explore whether continuing with LMWH is
something that is acceptable to patients and their health care professionals and if there
are any side effects with continuing LMWH.
The research team is made up of experienced researchers from all health care settings (GPs,
hospital doctors and nurses and health care professionals working in charity organisations).
They are supported by approved clinical trials units, which are experienced in running large
studies in all areas. The team members also have links to many national and international
professional, policy and patient groups, which will be essential to help report the findings
of this study.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Number of eligible and recruited patients (target recruitment rate of 30% of eligible patients) over 12 months, and proportion of participants with recurrent VTEs during follow-up.
Simon Noble, Dr
United Kingdom: Medicines and Healthcare Products Regulatory Agency