COPE-trial: Colesevelam versus placebo in cholestatic pruritus, a double-blind placebo-controlled study

Pathofysiology of pruritus secundary to cholestasis remains largely unknown but
it is generally believed that bile acids are etiologically involved. The
principal pharmacological treatment options currently available are
cholestyramine (a non-absorbable bile-acid binding resin), rifampicin and
naltrexon. The efficacy of these drugs is limited and side-effects are common,
in particular obstipation and nausea (cholestyramine), interaction with other
treatments and toxic effects on the liver (rifampicin), and endogenous
opioid-withdrawal syndrome (naltrexon). In addition, the efficacy of
cholestyramine has never been investigated by placebo-controlled trials. This
makes treatment of cholestatic pruritus frequently problematic and
unsatisfactory. New treatment options are urgently needed.
Colesevelam (Cholestagel) seems a highly interesting new option. It is a bile
acid sequestrant much more potent than cholestyramine but reportedly with an
incidence of side-effects comparable to that of placebo. However, until now the
efficacy of colesevelam in cholestatic pruritus has not been (adequately)
tested.

Pruritus is a frequent and debilitating symptom in patients with Primary
Biliary Cirrhosis, Primary Sclerosing Cholangitis and other cholestatic liver
diseases. Aim is to assess the effect of Colesevelam on cholestatic pruritus.

At least 38 patients with cholestatic pruritus will be included in an
investigator-initiated, multicenter, double-blind, placebo-controlled trial.
Patients will be treated with study medication (either colesevelam or placebo)
for 3 weeks.

Treatment with effective agent (colesevelam) or placebo

Adverse events of Colesevelam are comparable to those of placebo and cause
limited burden.
Major risk for patients is to be withhold from anti-pruritic therapy for a
maximum of 6 weeks.
3 weeks in case of a wash-out period for cholestyramine, another 3 weeks if
randomized for placebo.
On the other hand, especially people who still have pruritus despite current
therapy will tend to participate in this trial. For these patients
participation might be beneficial.
Participation to this study is time-consuming, since a diary and questionnaires
have to be filled out. This can be done at home or at out-patient clinic.
Participant won't be admitted to the hospital.