Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition (ABSORB)

Universitaire Ziekenhuizen KU Leuven

Status and phase: Enrolling; Phase 4

Conditions: Anticoagulation; Short Bowel Syndrome

Treatments: Drug: Apixaban steady-state; Drug: Apixaban single dose

Study type: Interventional

Funder types: Other

Identifiers

NCT04344717

s63950

Details and patient eligibility

About

Short bowel syndrome (SBS) is defined as a loss of function of the small intestine resulting in a malabsorptive disorder. In SBS, oral drug absorption may be altered due to extensive intestinal resection. It remains unclear to what extent apixaban exposure is impacted in SBS.Therefore this study tries to investigate the pharmacokinetics (PK) of apixaban in adult patients with SBS requiring long-term parenteral nutrition (PN).

Enrollment: 84 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria SBS single dose:

• patients with SBS (small bowel length of <2m after Treitz ligament) on long term (>3 months) PN or fluids who are apixaban-, vitamin K antagonist- and teduglutide naive

Inclusion criteria SBS steady-state:

• patients with SBS (small bowel length of <2m after Treitz ligament) on long term (>3 months) PN or fluids who are teduglutide naive and who are already taking apixaban 2,5 mg or 5 mg twice daily for ≥ 4 days

Inclusion criteria non-SBS single dose:

• healthy individuals without history of GI resections or other conditions associated with impaired absorption, who are apixaban- and vitamin K antagonist naive

Inclusion criteria non-SBS steady-state:

• patients without history of gastrointestinal resections or other conditions associated with impaired absorption (= controls), who are already taking apixaban 2,5 mg or 5 mg twice daily for ≥ 4 days

Exclusion criteria SBS (single dose+ steady-state):

• <18 years
• non-Dutch speaking
• recent (<6 months) major bleeds according with the International Society on Thrombosis and Haemostasis definition of major bleeding in non-surgical patients (20)
• creatinine clearance of < 15 mL/min or dialysis dependent
• liver failure classified as Child Pugh C
• total bilirubin ≥ 1.77 mg/dL (= 1,5 x upper limit of normal)
• presence of coagulopathy and a clinically relevant bleeding risk
• pregnancy or lactation
• concomitant intake of strong combined inhibitors of CYP3A4 and P-gp
• participation in a recent (<1 month) trial with an investigational product
• recent (<6 months) gastrointestinal surgery
• gastrointestinal mucosal disease interfering with absorption (e.g. radio-enteritis, inflammatory bowel disease, celiac disease, ...)
• gastrointestinal fistulae
• SBS with intestinal failure resulting from gastric bypass surgery

Exclusion criteria non-SBS (single dose+ steady-state):

• <18 years
• non-Dutch speaking
• recent (<6 months) major bleeds according with the International Society on Thrombosis and Haemostasis definition of major bleeding in non-surgical patients (20)
• creatinine clearance of < 15 mL/min or dialysis dependent
• liver failure classified as Child Pugh C
• total bilirubin ≥ 1.77 mg/dL (= 1,5 x upper limit of normal)
• presence of coagulopathy and a clinically relevant bleeding risk
• pregnancy or lactation
• concomitant intake of strong combined inhibitors of CYP3A4 and P-gp
• use of prokinetics, antimotility drugs or opioids
• participation in a recent (<1 month) trial with an investigational product

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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84 participants in 5 patient groups

Anticoagulation and teduglutide naive short bowel syndrome

Experimental group

Description:

Apixaban-, vitamin K antagonist- and teduglutide naive patients with short bowel syndrome requiring long term parenteral support

Treatment:

Drug: Apixaban single dose

Healthy volunteers

Experimental group

Description:

Apixaban- and vitamin K antagonist naive healty volunteers

Treatment:

Drug: Apixaban single dose

Short bowel syndrome on apixaban

Other group

Description:

Patients with short bowel syndrome requiring long term parenteral support and taking apixaban 2.5 mg twice daily or 5 mg twice daily

Treatment:

Drug: Apixaban steady-state

Patients with a normal gastrointestinal tract on apixaban

Other group

Description:

Patients with a normal gastrointestinal tract taking apixaban 2.5 mg twice daily or 5 mg twice daily

Treatment:

Drug: Apixaban steady-state

Anticoagulation naive short bowel syndrome on teduglutide

Experimental group

Description:

Apixaban- and vitamin K antagonist naive patients with short bowel syndrome requiring long term parenteral support and initiated on teduglutide

Treatment:

Drug: Apixaban single dose