Improved Adherence With Extended Venous Thromboembolism Prophylaxis After Major Cancer Surgery

Towards Improved Adherence With Extended Venous Thromboembolism Prophylaxis After Abdominal or Pelvic Major Cancer Surgery

This is a prospective, twin-center, cohort study in patients discharged from the hospital after major abdominal or pelvic cancer surgery for cancer. This study is designed to evaluate the adherence to extended deep vein thrombosis prophylaxis (DVT) with the direct oral anticoagulant apixaban on the background of historical data from the investigator's center on low-molecular-weight heparin (LMWH) substandard adherence in the same setting.

Study Overview

• Status: Completed
• Conditions: Surgery; Venous Thromboembolism; Adherence, Medication; Prophylaxis; Neoplasms Malignant
• Intervention / Treatment: Drug: Apixaban 2.5 milligram

Detailed Description

All guidelines have embraced the concept of extended DVT prophylaxis after major abdominal or pelvic surgery for cancer, but the recommendation is consistently to use LMWH, which is more complicated than orally available prophylaxis, more expensive and has poor adherence.

The patients will be identified in the pre-operative admission or in post-operative orders as potentially eligible for extended prophylaxis. On the day of discharge a research assistant or a research nurse will approach the patient, provide information about the study and obtain written consent if the patient fulfills the eligibility criteria.

Each patient will be asked to take apixaban until postop day 29±1 and will be followed until postop day 90±3. The total duration of the study from first patient in to last patient out is expected to take 12 months.

At 1 week after discharge there is a telephone contact to ask about any side effects from apixaban or bleeding events or signs of thromboembolism and to answer any questions from the patient.

At postoperative Day +28-30 there is a telephone contact to ask about side effects, bleeding, signs of venous thromboembolism (VTE), until what date the patient has taken apixaban and estimate of missed doses using a standardized script. If the patient is still taking it, instruction will be given to discontinue. Self-reported modified Morisky Medication Adherence scale with 6 statements will be used At 90 days ±3 days there is the last telephone contact to ask about bleeding events or signs of VTE. The study is complete for the patient. At the time of Visit 4 the pharmacy that the patient uses will be contacted to provide dispensing record for apixaban, in order to verify that the patient filled the prescription.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Thrombosis Service, HHS-General Hospital
    • Hamilton, Ontario, Canada, L8V 1C3
      • HHS-Juravinski Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of at least 18 years of age, discharged after hepato-biliary, colorectal or gynecology-oncology abdominal/pelvic surgery (laparoscopic or open) for cancer and considered at increased risk for VTE (e.g. previous history of VTE, residual cancer, slow mobilization, obesity, comorbidities).
• Written informed consent obtained.

Exclusion Criteria:

• Patient unable to take tablets, even if crushed.
• Active bleeding.
• Venous thromboembolism diagnosed during the hospitalization.
• Severe hepatic impairment (Child Pugh class C).
• Severe renal failure on dialysis or with calculated creatinine clearance <15 mL/min.
• Platelet count <50·109/L.
• Concomitant treatment with azole-antimycotics, e.g., ketoconazole, itraconazole, voriconazole, or posaconazole, and HIV protease inhibitors, e.g., ritonavir.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apixaban; apixaban for extended prophylaxis against VTE after discharge	Drug: Apixaban 2.5 milligram; apixaban 2.5 milligram twice daily from discharge until postoperative day 29 +/- 1 day; Other Names: medication adherence assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Filled prescription	Percent of included patients that have filled their prescription for apixaban	1 week
At least 80% adherence	Percent of patients with filled prescription that have at least 80% adherence	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Venous thromboembolism post prophylaxis	The event rate of venous thromboembolism during the 2 months after planned prophylaxis	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Venous thromboembolism during prophylaxis	Symptomatic, objectively verified deep vein thrombosis of pulmonary embolism during 1st month	30 days
Rate of Major bleeding during prophylaxis	Major bleeding during 1st month	30 days
Rate of Clinically relevant non-major bleeding during prophylaxis	Clinically relevant non-major bleeding during 1st month	30 days
Rate of Death during prophylaxis	Death during 1st month	30 days

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Sam Schulman, MD, PhD, Dr.

Publications and helpful links

General Publications

• Serrano PE, Parpia S, Valencia M, Simunovic M, Bhandari M, Levine M. Incidence of delayed venous thromboembolic events in patients undergoing abdominal and pelvic surgery for cancer: a systematic review and meta-analysis. ANZ J Surg. 2019 Oct;89(10):1217-1223. doi: 10.1111/ans.15290. Epub 2019 Jun 18.
• Serrano PE, Parpia S, Linkins LA, Elit L, Simunovic M, Ruo L, Bhandari M, Levine M. Venous Thromboembolic Events Following Major Pelvic and Abdominal Surgeries for Cancer: A Prospective Cohort Study. Ann Surg Oncol. 2018 Oct;25(11):3214-3221. doi: 10.1245/s10434-018-6671-7. Epub 2018 Jul 26.
• Schulman S, Carlson V, Serrano PE, Sne N, Kahnamoui K, Mithoowani S, Ikesaka R, Gross PL. Adherence to apixaban for extended thromboprophylaxis after major abdominal or pelvic surgery for cancer: A prospective cohort study. J Surg Oncol. 2022 Aug;126(2):386-393. doi: 10.1002/jso.26876. Epub 2022 Apr 1.

Helpful Links

• Publication of the study

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2021
• Primary Completion (Actual): October 31, 2021
• Study Completion (Actual): November 6, 2021

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: abdominal; apixaban; pelvic
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Neoplasms; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: 10768

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes