Controlling Glucose during Elective hip Surgery to study the influence on Coagulation

During orthopedic surgery, the coagulation system is activated, resulting in a
considerable risk of postoperative venous thromboembolism (VTE). Additionally,
increased postoperative glucose levels (> 7.9 mmol/l) are related to an
increased number of symptomatic VTE, independent of known diabetes mellitus
and other confounders. Evidence is mounting that hyperglycemia during surgery
due to stress of the procedure (*stress hyperglycemia*), leads to a
hypercoagulable and hypofribinolytic state. No intervention studies have
investigated the influence of glycemic control during hip surgery on
coagulation activation. The most widely used method to apply glycemic control
is intensive insulin therapy. This carries however an increased risk of
hypoglycemia related mortality. As most hip surgery is elective, applying
glycemic control using other glucose lowering agents with less risk to develop
hypoglycemia is a possibility. A recent development in glucose lowering agents
is the availability of incretins. Liraglutide, a human glucagon-like peptide
(GLP-1) analogue, increases insulin secretion and decreases glucagon secretion
in a glucose-dependent manner and is an approved drug in the management of
diabetes mellitus type 2.

the purpose of this study is to investigate the efficacy of liraglutide to
lower glucose and to influence coagulation activation during and after hip
surgery

A prospective, randomized, double-blind, placebo-controlled trial

The participants will be randomized to one of the two treatment groups, the
liraglutide group (LG) or the control group (CG). Subjects in the LG will start
one day prior to surgery with administration of liraglutide subcutaneously
(s.c.) once daily, this will be continued until three days postoperatively.
Start dosing will be 0.6 mg, this will be intensified to 1.2mg if there is no
nausea on the starting dose. The CG will be given placebo s.c. one day prior to
surgery until three days postoperatively. The study will end three days
postoperatively.

The study will be conducted on patients who will undergo elective hip surgery.
Informed consent will be obtained beforehand during the screening visit. The
study will be performed peri-operatively, therefore no extra hospital visits
are expected. Before induction of anaesthesia, 2 hours after surgery and three
days after surgery blood samples will be obtained (a 2ml Sodium-Floride tube
and three 2.7mL Sodium-Citrate-tubes and a 6mL heparin tube) to measure
glucose, coagulation parameters, cortisol and glucagon levels.HbA1C measurement
(a 4,5 ml heparin tube) will be obtained once before induction of anaesthesia.
A maximum of 53mL blood loss during the study will be expected. Participation
will provide no direct immediate benefit to patients. Common adverse events
with liraglutide treatment are related to the gastrointestinal system, nausea
as reported most frequently. Other adverse events include upper respiratory
tract infections and headache. All adverse events are mostly mild and the
drop-out rate from clinical trials due to adverse events has been low. The
study will provide more insight in the effect of a GLP-1 receptor agonist as a
glucose lowering agent in peri-operative setting and its influence on
coagulation activation. This insight may help to find an optimal glycemic
control strategy to diminish activation of coagulation and/or impairment of
fibrinolysis and in the long run prevent VTE following hip surgery.