Anticoagulant treatment after knee arthroscopy or during plaster cast lower leg immobilisation: determining the balance between benefits and risks

Currently, guidelines and clinical practice differ considerably with respect to
use of anticoagulant treatment after arthroscopy of the knee or during cast
immobilisation of the lower leg. Trials that have been carried out were aimed
at efficacy only, had small sample sizes and therefore mainly used asymptomatic
thrombosis as endpoint. From these trials an overall risk benefit-balance could
not be established, hence the current controversy exists. In the proposed study
we will use relevant symptomatic endpoints in a large cohort of patients.
Furthermore we will follow subjects with an adverse event for a longer period,
during which we will assess the long term sequelae of these events. Lastly, we
will determine high risk groups that will benefit most from anticoagulant
treatment.

Comparative effectiveness research to determine cost-effectiveness of an
existing healthcare policy, i.e. treatment with low molecular weight heparin
(LMWH) after knee arthroscopy and lower leg plaster cast immobilization
following surgical or conservative treatment. In addition we will investigate
personalized prophylaxis based on genetic and acquired risk factors these
groups at high risk of venous thrombosis.

Two parallel randomised controlled trials comparing a policy with the
anticoagulant LMWH to a policy with no anticoagulant in two groups of patients
with an increased risk of venous thrombosis: patients who underwent knee
arthroscopy and patients with lower leg cast immobilisation.
In both trials determination of genetic and acquired risk factors will be
performed at the start of the study. Based on the presence or absence of these
factors we will assign a risk profile to each patient.

In case of knee arthroscopy: LMWH (nadroparin 2850 IE s.c. once daily, > 100kg
5700IE sc) for 8 days vs no treatment. In case of lower leg plaster cast
immobilization: LMWH (nadroparin 2850 IE s.c. once daily, > 100kg 5700IE sc)
for the duration of the immobilisation (average 6-8 weeks) vs no treatment.

Blood taken pre- and post-operatively or at the emergency department will be
analysed on 5 common single nucleotide polymorphisms (SNPs) known to strongly
affect thrombotic risk; on levels of 7 coagulation factors in plasma (of which
high or low levels are known to increase the risk). Patients will also be
screened on acquired risk factors for thrombosis through a questionnaire.

We will compare two standard treatment modes that are currently both given
depending on the physician*s or hospital*s preference. The patients in our
trial will be subjected to one of these standard treatments. It is therefore
not expected that participation will lead to an increased health risk.
Nadroparin is not an experimental pharmaceutical. Not participating in the
trial may, depending on the physician, still lead to treatment with Nadroparin.
All patients will need to undergo one venapuncture for blood sampling for the
study. In case of surgical treatment this blood sample will be taken
pre-operatively. Another blood sample will be taken post-operatively but does
not require an extra venapuncture because it will be taken from the intravenous
catheter.In case of cast immobilisation this blood sample will be taken at the
first day of immobilisation.
No extra hospital visits are required. Patients who had an arthroscopy of the
knee will be, on top of regular follow-up vistis, contacted by telephone after
three months, to make sure no complications will be missed. Patients with lower
leg cast immobilisation will be contacted by telephone at three weeks and three
months (besides regular follow-up visitis), due to the wide variance in
treatment and follow-up.
One questionnaire concerning risk factors for thrombosis, bleeding and patients
demographics will be filled in before arthroscopy or at the first day of cast
immobilisation.
Only subjects with (serious) adverse events (and a similar random sample of
subjects without a (serious) adverse event) will be monitored for a two year
period after the event. After six months, one year and two years after the
event, patients will be seen for clinical examination and quality of life
assessment by means of a questionnaire.