CLOTBUST-L
An open-label, multicentre, randomised controlled trial to evaluate the efficacy of ex situ fibrinolysis during normothermic perfusion in liver transplantation from donation after circulatory death donors
Chief investigator: Mr Vasilis Kosmoliaptsis
Study sponsor: The University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
Funder: NIHR [NIHR161200]
Study background
Liver transplantation is a life-saving treatment for patients with severe liver disease. However, many donor livers go unused when there are concerns that the liver will not work or will develop serious complications.
One complication occurs when small clots form in the blood supply to the bile ducts (the tubes that drain bile in the liver to the gut). This causes scarring, which blocks the flow of bile. The resulting stagnant bile becomes infected, and this leads to more scarring.
This is called "cholangiopathy" and often needs repeated hospital admissions for treatment; severe cases will need a liver re-transplant.
The small clots that cause cholangiopathy are more common in Donation after Circulatory Death (DCD) donor livers.
Cholangiopathy may be prevented by dissolving the clots that cause the bile duct damage using clot-buster drugs: the clot-buster treatment can be given to the liver while it is on a perfusion machine outside the body before transplantation, to clear the clots and prevent bile duct problems after the transplant.
Some DCD livers will receive the clot-busting treatment and machine perfusion, and others will be treated as they are now, so we can find out if the treatment works.
Study objective
The CLOTBUST-L trial will assess whether ex situ fibrinolysis during normothermic machine perfusion of DCD livers reduces the incidence of symptomatic cholangiopathy, in comparison to the current standard of care.
Study design
The CLOTBUST-L trial is a phase III, open label, randomised controlled superiority trial.
DCD donor livers will be randomised to the participating centre's standard treatment for DCD livers or to receive machine perfusion plus the "clot-buster" drug and fresh frozen plasma, prior to transplantation.