Apixaban for Inflammatory Bowel Disease

(EXPAND Trial)

Recruiting at 1 trial location

Overseen By Tyler McKechnie, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: McMaster University

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

Disqualifiers: VTE history, Severe renal impairment, others

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug Apixaban can prevent blood clots in people with inflammatory bowel disease (IBD) after abdominal surgery. It focuses on preventing deep vein thrombosis (DVT) and pulmonary embolism (PE), which occur more frequently in IBD patients post-surgery. Participants will receive either Apixaban or a placebo (a pill with no active drug) to compare outcomes. This trial is suitable for individuals with Crohn's disease or ulcerative colitis undergoing planned abdominal surgery at specific hospitals. As an Early Phase 1 trial, this research seeks to understand how Apixaban works in people, offering participants a chance to contribute to groundbreaking medical knowledge.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that apixaban is generally safe for many patients, including those with inflammatory bowel disease (IBD). However, specific considerations are necessary. People with IBD might face a higher risk of digestive tract bleeding when taking apixaban due to small sores called mucosal erosions. Compared to warfarin, another blood thinner, apixaban presents a lower risk of serious bleeding in individuals with conditions like Crohn's disease and ulcerative colitis, which are similar to IBD.

These findings suggest that while apixaban is usually well-tolerated, individuals with IBD should be aware of the potential for increased bleeding. Consulting a healthcare provider about these risks and benefits is important before starting any new treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for Inflammatory Bowel Disease (IBD) that primarily rely on immunosuppressants and biologics to control inflammation, apixaban is unique because it targets blood clotting pathways. Researchers are excited about apixaban for IBD as it may reduce inflammation by preventing small blood clots that can worsen bowel damage. This novel approach could offer an alternative for patients who don't respond well to conventional therapies, potentially providing quicker relief with a different mechanism of action.

What evidence suggests that apixaban might be an effective treatment for reducing postoperative VTE in IBD patients?

Research shows that people with inflammatory bowel disease (IBD) have a higher risk of developing blood clots, such as deep vein thrombosis (DVT) or pulmonary embolism (PE), especially after surgery. Studies have found that direct oral anticoagulants, such as apixaban, can lower these risks. In this trial, participants in the experimental arm will receive apixaban, which previous research has shown to reduce the likelihood of clot-related issues more effectively than traditional blood thinners like warfarin. It also tends to cause less bleeding in people with IBD. By preventing blood clots, apixaban may offer significant benefits for IBD patients after surgery, leading to better safety and health outcomes. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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

My surgery will be at Hamilton Health Sciences or St. Joseph's Healthcare Hamilton.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Apixaban
• Placebo Oral Tablet

Trial Overview 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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

In a study involving 48 healthy subjects, apixaban was found to be safe and well-tolerated across a wide range of doses (2.5 to 25 mg), with no dose-limiting adverse events reported, indicating its potential for safe use in clinical settings.

The pharmacokinetics of apixaban showed predictable behavior, with maximum plasma concentrations reached approximately 3 hours after dosing and a dose-related increase in clotting times, suggesting effective anticoagulant action that correlates with drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Frost, C., Nepal, S., Wang, J., et al.[2022]

Apixaban is an effective oral anticoagulant that inhibits factor Xa, approved for various thromboembolic disorders, including stroke prevention in atrial fibrillation and treatment of deep vein thrombosis, with a bioavailability of about 50%.

The drug is rapidly absorbed and has a predictable pharmacokinetic profile across diverse patient populations, allowing for fixed dosing without the need for routine monitoring, and it shows minimal interactions with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review. Byon, W., Garonzik, S., Boyd, RA., et al.[2021]

Apixaban, a novel oral factor Xa inhibitor, has shown promise in preventing venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA), with a recommended dose of 2.5 mg twice daily established from a phase II trial.

In phase III trials, apixaban demonstrated non-inferiority to enoxaparin in one study (ADVANCE-2) while maintaining a similar safety profile, supporting its potential use for thromboprophylaxis after TKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of apixaban in the prevention of venous thromboembolism in patients undergoing total knee replacement surgery. Martin, MT., Nutescu, EA.[2012]

Apixaban is a highly selective factor Xa inhibitor that demonstrated potent anticoagulant properties in vitro, with a very low inhibition constant (K(i)) of 0.08 nm for human FXa, indicating its effectiveness in preventing blood clots.

In rabbit models, apixaban effectively prevented thrombosis at doses that did not significantly affect bleeding time, suggesting it can reduce clot formation while maintaining normal hemostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. Wong, PC., Crain, EJ., Xin, B., et al.[2023]

Apixaban is a highly effective oral anticoagulant that directly inhibits activated factor X, which plays a crucial role in blood clotting, and it also helps prevent platelet aggregation.

This medication has predictable pharmacokinetics, minimal food and drug interactions, and a wide therapeutic window, making it safe and convenient for patients, as it can be taken with or without food.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apixaban - Metabolism, Pharmacologic Properties and Drug Interactions. Kubisz, P., Stanciakova, L., Dobrotova, M., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10070226/

Effectiveness and Safety of Apixaban vs Warfarin in Patients ... For the two treatment cohorts, 20.7% of patients had a history of bleed and 5.4% had thrombocytopenia. Additionally, nearly 4.0% of patients had thrombophilia, ...

2. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1476/7967943

P0764 Are anticoagulants safe in patients with Inflammatory ... Inflammatory bowel disease (IBD) patients may have a higher risk of gastrointestinal bleeding during anticoagulant treatment due to mucosal erosions.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1470211825001010

Direct oral anticoagulants vs warfarin in patients with ... Subgroup analyses showed that outcomes were consistent across Crohn's disease and ulcerative colitis groups. DOACs consistently demonstrated a lower risk of ICH ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04344717

Pharmacokinetics of Apixaban in Patients With Short Bowel ... Study Details | NCT04344717 | Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition | ClinicalTrials.gov.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4194568/

Inflammatory bowel disease and thromboembolism - PMC To summarize, recent data show that patients with IBD, both CD and UC, are at an increased risk for ATEs, mainly CVA, IHD and mesenteric ischemia, albeit to a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12494242/

Comparative safety and effectiveness of apixaban and ... In this retrospective cohort study using U.S. Medicare and MarketScan data, we found that apixaban was associated with similar risk of recurrent ...

7. journals.lww.com journals.lww.com/ajg/fulltext/2024/10001/s1800_morbidity_and_mortality_of_cirrhotic.1801.aspx

S1800 Morbidity and Mortality of Cirrhotic Patients on... In our study, apixaban (including MELD scoring) had a higher overall morbidity and mortality percentage compared to rivaroxaban.