Apixaban for Inflammatory Bowel Disease

(EXPAND Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: McMaster University

Must not be taking: Anticoagulants, Antiplatelets, SSRIs, SNRIs

Disqualifiers: VTE history, Severe renal impairment, others

Trial Summary

What is the purpose of this trial?

Inflammatory bowel disease (IBD) is a relatively common disease that effects all age groups and carries significant morbidity and mortality. The initial treatment typically involves both short and long term medication, however when this is not enough to adequately control the disease, surgery is often required. The high morbidity and mortality rates are in part due to the increased rates of venous thromboembolism (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE) which have been shown to develop more frequently in IBD patients compared to the general population. Undergoing abdominal surgery has also been shown to independently increase rates of DVT and PE and since the majority of patients with IBD will undergo surgery at least once in their lifetime, the relative increased risk of developing a VTE is very high. The majority of DVT and PE events in the postoperative IBD population will occur after discharge from hospital and therefore carries significant morbidity and mortality risk in a unmonitored setting. Several studies have demonstrated the benefits and safety of twice daily dosing of oral extended VTE prophylaxis agents in orthopedic and cancer postoperative patients following discharge from hospital. There have been no randomized studies which have evaluated the use of extended postoperative VTE prophylaxis in IBD patients. The purpose of this randomized placebo controlled pilot trial will be to evaluate the efficacy and safety of postoperative VTE prophylaxis in IBD patients following abdominal surgery. If this pilot trial demonstrates efficacy in reducing postoperative DVT and PE rates, safety and feasibility, clinicians will be armed with the knowledge to pursue a larger multicenter randomized trial with the intent of reducing overall morbidity and mortality in this high risk population.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to join this trial. Specifically, if you are on strong inhibitors or inducers of CYP 3A4 and P-gp, drugs affecting blood clotting, or any anticoagulants, you would not be eligible to participate.

How does the placebo drug differ from other treatments for inflammatory bowel disease?

The placebo drug used in the trial is a dummy pill with no active ingredients, unlike other treatments for inflammatory bowel disease that contain active substances designed to reduce inflammation or suppress the immune system.

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Eligibility Criteria

This trial is for adults with Crohn's disease or ulcerative colitis who are undergoing elective abdominal surgery at specific hospitals. They must not be pregnant, have a history of blood clots, liver disease with bleeding risk, or be on certain drugs like strong CYP3A4 inhibitors/inducers and anticoagulants.

Inclusion Criteria

I am planning to have surgery that is not an emergency.

I am 18 years old or older.

I have been diagnosed with Crohn's disease or ulcerative colitis.

Exclusion Criteria

I need surgery urgently.

I am not willing or able to use birth control during the treatment.

I am not currently experiencing any serious bleeding.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive twice daily dosing of apixaban or placebo starting on the first day of hospital discharge

3 months

Regular follow-up visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of VTE and bleeding events

3 months

Participant Groups

The study tests if taking Apixaban (a blood thinner) after surgery can prevent blood clots better than a placebo in IBD patients. It's randomized and placebo-controlled to compare the effectiveness and safety of extended postoperative clot prevention.

Group I: Experimental Experimental Treatment 1 Intervention

The treatment arm will receive a full supply of twice daily 2.5 milligram (mg) dosing of apixaban beginning on the first day of hospital discharge.

Group II: Placebo Placebo Group 1 Intervention

The placebo group will receive a similarly appearing full supply of a twice daily placebo oral tablet.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

St. Joseph's Healthcare Hamilton, Canada

Juravinski Hospital Hamilton, Canada

Who Is Running the Clinical Trial?

McMaster University Lead Sponsor

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review. [2021] Apixaban is an oral, direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa, and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism. The absolute oral bioavailability of apixaban is ~ 50%. Food does not have a clinically meaningful impact on the bioavailability. Apixaban exposure increases dose proportionally for oral doses up to 10 mg. Apixaban is rapidly absorbed, with maximum concentration occurring 3-4 h after oral administration, and has a half-life of approximately 12 h. Elimination occurs via multiple pathways including metabolism, biliary excretion, and direct intestinal excretion, with approximately 27% of total apixaban clearance occurring via renal excretion. The pharmacokinetics of apixaban are consistent across a broad range of patients, and apixaban has limited clinically relevant interactions with most commonly prescribed medications, allowing for fixed dosages without the need for therapeutic drug monitoring. The pharmacodynamic effect of apixaban is closely correlated with apixaban plasma concentration. This review provides a summary of the pharmacokinetic, pharmacodynamic, biopharmaceutical, and drug-drug interaction profiles of apixaban. Additionally, the population-pharmacokinetic analyses of apixaban in both healthy subjects and in the target patient populations are discussed.

2. England pubmed.ncbi.nlm.nih.gov

Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. [2023] Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Apixaban - Metabolism, Pharmacologic Properties and Drug Interactions. [2018] Apixaban is an oral, potent, highly selective, reversible and direct inhibitor of activated coagulation factor X, that is the end point of the intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the capacity to indirectly inhibit thrombin-induced platelet aggregation. This new oral anticoagulant represents an immediate-release form of peroral drug with quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset and offset of action. No clinically relevant age- or sex-dependent difference in the apixaban pharmacokinetics and pharmacodynamics which would lead to the modification of the dose exists, apixaban may even be administered with or without food. Its elimination is mediated by metabolism, renal elimination of unmodified drug and excretion in the gastrointestinal tract.

4. England pubmed.ncbi.nlm.nih.gov

Therapeutic potential of apixaban in the prevention of venous thromboembolism in patients undergoing total knee replacement surgery. [2012] Apixaban is a novel oral factor Xa inhibitor that recently completed evaluation in clinical trials for its use in the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery. Its manufacturers are currently seeking approval for these indications in the European Union and a rolling submission is in process in the United States.

5. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. [2022] Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban.