EvaluaTion of Clinical and laboratory outcomes of Rivaroxaban in short Bowel syndrome patients dEpending on Long term parenteral nutrition: a prospective cohort study

Rationale

Short bowel syndrome patients are patients at high risk for thrombosis ánd bleeding. In a recent retrospective cohort of 266 patients, 11% developed a recurrent thrombosis and 4.3% developed a bleeding complication within one year. In recent years, direct oral anticoagulants (DOACs) have emerged as a first-line option for the treatment and prevention of venous thromboembolism. A prior pilot study showed that the DOAC rivaroxaban is well absorbed in most patients, but not in all. Therefore in AMC patients with short bowel syndrome, with a lifelong indication for anticoagulation who are prescribed rivaroxaban 20 mg 1dd1, regular “absorption checks” are performed as clinical routine to assure that the adequate plasma levels are obtained . However, in this specific patient population there is no data yet on clinical outcomes showing the relation between the DOAC plasma levels and therapeutic efficacy. This study is conducted to test the following hypotheses:

1) Adequate plasma levels (anti Xa levels and drug concentration) of rivaroxaban in a patient population suffering from short bowel syndrome correlate with favorable clinical outcomes, in particular less recurrent thrombosis.

2) Rivaroxaban in patients suffering from short bowel syndrome who have a lifelong indication for anticoagulants leads towards improvement of quality of life.

Objective

1) To evaluate attained rivaroxaban plasma levels, assessed anti Xa levels and drug concentration, in patients with short bowel and to relate these blood levels to clinical outcomes.

2) To evaluate the change in quality of life in this patient population.

Study design and population

We choose to perform a prospective cohort drug study with minimally invasive measurements where patients with short bowel syndrome who are taking rivaroxaban according to clinical routine will be observed during a period of at least one year. Patients ≥ 18 years old are eligible for the study if they are diagnosed with SBS by the AMC outpatient clinic endocrinology, if they have a DOAC-registered indication for life long anticoagulants (atrial fibrillation, thromboprophylaxis and treatment of VTE) and if they have no contra-indications for DOAC’s. The invasive measurements consist of 12 extra blood drawls and 2 SF-36 quality of life questionnaires over a period of half a year. The intervention is not the prescribing of rivaroxaban as rivaroxaban is prescribed for the indication which it was registered for.

Main study parameters/endpoints:

- Clinical outcomes: VTE, bleeding, mortality- Laboratory outcomes: anti Xa levels and plasma concentrations of rivaroxaban

- SF-36 questionnaire

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no specified burden or risks associated with participation, as in clinical scenario the same assessments would be done, except for 4 extra blood drawls per day (and filling in two SF-36 questionnaires on quality of life. As it is a drug study, a moderate risk has been assigned to this study.

Rivaroxaban in patients with short bowel syndrome is absorbed well and improves quality of life.

T0 = baseline

T1 = 3 months

T2 = 6 months

Blood samples (pharmacokinetic profile) and quality of life questionnaires