ABSORB: Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Short bowel syndrome Single dose administration of 2.5 mg and 5 mg (1 week wash out between 2 doses) apixaban to patients with short bowel syndrome requiring long term parenteral nutrition |
Drug: Apixaban single dose
A single dose of apixaban 2.5 mg and/or 5 mg will be administered and PK characteristics will be measured
Other Names:
|
| Other: Normal gastrointestinal tract Single dose administration of 2.5 mg or 5 mg apixaban to patients with a normal gastrointestinal tract with an indication for anticoagulation with apixaban (atrial fibrillation). |
Drug: Apixaban single dose
A single dose of apixaban 2.5 mg and/or 5 mg will be administered and PK characteristics will be measured
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Difference in Cmax of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate the difference in peak level (Cmax) after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN
Secondary Outcome Measures
- Difference in estimated trough level (Cmin) of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate differences in estimated Cmin (12h after administration) after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN
- Difference in time to reach Cmax (Tmax) of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate differences in Tmax after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN
- Difference in exposure (AUC0-12h) of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate differences in AUC0-12 after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN
- Difference in absorption rate constant of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate the difference in absorption rate constant between patients with and without SBS requiring long-term PN
- Difference in bioavailability of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate the difference in bioavailability between patients with and without SBS requiring long-term PN
- Difference in volume of distribution of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate the difference in volume of distribution between patients with and without SBS requiring long-term PN
- Difference in clearance of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate the difference in clearance between patients with and without SBS requiring long-term PN
- Difference in half-life of apixaban between SBS patients and patients with a normal gastrointestinal tract [Through study completion, an average of 1.5 years]
To investigate the difference in half-life between patients with and without SBS requiring long-term PN
- To set up an optimized dosing scheme of apixaban for SBS patients [Through study completion, an average of 1.5 years]
To set up an optimized dosing scheme of apixaban, using PK modeling, for SBS patients taking into account identified covariates (eg. sex, age, race...) and PK measurements from outcome 1-9.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
SBS patients: patients with SBS (small bowel length of <2m after Treitz ligament) on long term (>3 months) PN or fluids who are anticoagulation naive
-
normal gastrointestinal tract patients: patients without history of gastrointestinal resections or other conditions associated with impaired absorption (= controls), who are anticoagulation naive and have to start anticoagulation for non-valvular atrial fibrillation with apixaban 2,5 mg or 5 mg twice daily
Exclusion Criteria:
-
for both groups:
-
<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
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liver failure classified as Child Pugh C
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total bilirubin ≥ 1.77 mg/dL (= 1,5 x upper limit of normal)
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presence of coagulopathy and a clinically relevant bleeding risk
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pregnancy or lactation
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concomitant intake of other anticoagulant agents
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concomitant intake of strong combined inhibitors of CYP3A4 and P-gp
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participation in a recent (<3 months) trial with an investigational product
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for SBS patients only:
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recent (<6 months) gastrointestinal surgery
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gastrointestinal mucosal disease interfering with absorption (e.g. radio-enteritis, inflammatory bowel disease, celiac disease, …)
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gastrointestinal fistulae
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SBS with intestinal failure resulting from gastric bypass surgery
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals Leuven | Leuven | Belgium | 3000 |
Sponsors and Collaborators
- Universitaire Ziekenhuizen Leuven
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Eikelboom JW, Quinlan DJ, Hirsh J, Connolly SJ, Weitz JI. Laboratory Monitoring of Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation: A Review. JAMA Cardiol. 2017 May 1;2(5):566-574. doi: 10.1001/jamacardio.2017.0364. Review.
- Jeppesen PB. Spectrum of short bowel syndrome in adults: intestinal insufficiency to intestinal failure. JPEN J Parenter Enteral Nutr. 2014 May;38(1 Suppl):8S-13S. doi: 10.1177/0148607114520994. Epub 2014 Jan 31. Review.
- Santamaría MM, Villafranca JJA, Abilés J, López AF, Rodas LV, Goitia BT, Navarro PU. Systematic review of drug bioavailability following gastrointestinal surgery. Eur J Clin Pharmacol. 2018 Dec;74(12):1531-1545. doi: 10.1007/s00228-018-2539-9. Epub 2018 Aug 22.
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