Postoperative Extended Venous Thromboprophylaxis in Inflammatory Bowel Disease

NCT03935451 | Unknown Early Phase 1 DMC

• 1 other identifier: 7043
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

IBD; Venous Thromboembolism; Crohn Disease; Ulcerative Colitis; Pulmonary Embolism; Colorectal Disorders

Outcome Measures

Primary Outcomes (2)

• Incidence of post operative venous thromboembolism events (DVT/PE) in in patients with Inflammatory Bowel Disease

  The primary efficacy outcome will be a composite of symptomatic proximal DVTs of the upper and lower extremities, splanchnic VTE, nonfatal PE (segmental or greater artery), and death from PE and death from any cause within 3 months following hospital discharge.

  3 months post operatively

• Incidence of bleeding while undergoing treatment with oral anticoagulant or placebo.

  The primary safety outcome will be bleeding reported during treatment, including major bleeding, clinically relevant non-major (CRNM) bleeding, minor bleeding, and the composite of major bleeding and CRNM bleeding.

  3 months post operatively

Secondary Outcomes (1)

• Incidence of surgical complications related to post operative anticoagulation

  3 months post operatively

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo Oral Tablet

Experimental

EXPERIMENTAL

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.

Drug: Apixaban 2.5 milligram

Interventions

Apixaban 2.5 milligram DRUG

2.5 milligram daily dosing of Apixaban beginning on the first day of hospital discharge for a total of 30 days

Experimental

Placebo Oral Tablet DRUG

placebo oral tablet that resembles the experimental drug. To be taken with the same frequency and duration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years old
• Having documented pathological diagnosis of either Crohn's disease or ulcerative colitis.
• Open or laparoscopic abdominal gastrointestinal surgery
• Elective surgery
• Surgery occurring at Hamilton Health Sciences or St. Joseph's Healthcare Hamilton
• Negative urine beta-hCG for women of childbearing potential

You may not qualify if:

• Contraindication to use of postoperative thromboprophylaxis (ie. Previous bleeding on anticoagulation)
• Allergy to apixaban
• History of VTE
• Current clinically significant active bleeding, including GI bleeding
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
• Severe renal impairment (eCrCl \<30 ml/min), or undergoing dialysis
• Lesions or conditions at increased risk of clinically significant bleeding (e.g. recent GI bleeding, recent ischemic or hemorrhagic cerebral infarction, active ulcerative GI disease, recent brain, spinal or ophthalmological surgery, bronchiectasis or history of pulmonary bleeding, thrombocytopenia or functional platelet defects, congenital or acquired coagulation disorder)
• Receiving any of the following drugs:
• Strong inhibitors of both CYP 3A4 and P-gp, such as azole-antimycotics (e.g. ketoconazole, itraconazole, voriconazole, or posaconazole), and HIV protease inhibitors (e.g. ritonavir)
• Strong inducers of both CYP 3A4 and P-gp (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's Wort)
• Drug products affecting hemostasis (e.g. NSAIDs, ASA or other antiplatelet agents \[e.g. ASA, clopidogrel, prasugrel, ticagrelor\], SSRIs, or SNRIs)
• Any other anticoagulant, including unfractionated heparin, LMWH, heparin derivatives, or oral anticoagulants (e.g. warfarin, dabigatran, rivaroxaban)
• Currently receiving therapy for any type of malignancy (e.g. colorectal, breast, lung)
• History of colorectal cancer
• Emergency surgery

Sponsors & Collaborators

• McMaster University: lead

Study Sites (2)

St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

Juravinski Hospital

Hamilton, Ontario, L8V 1C3, Canada

RECRUITING

MeSH Terms

Conditions

Venous Thromboembolism; Crohn Disease; Colitis, Ulcerative; Pulmonary Embolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Central Study Contacts

Cagla Eskicioglu, MD MSc

CONTACT

(905) 522-1155; eskicio@mcmaster.ca

Tyler McKechnie, MD

CONTACT

(905) 522-1155; tyler.mckechnie@medportal.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: May 2, 2019
• Study Start: September 1, 2021
• Primary Completion: December 31, 2025
• Study Completion: February 1, 2026
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)