Prolonged Hypercoagulability Following Major Liver Resection for Malignancy (PRIORITY)

This clinical trial will investigate the ability of thromboelastrogrpahy (TEG®) to detect hypercoagulability after liver surgery and will examine the effect of extended thromboprophylaxis (medical treatment to prevent the development of blood clots inside blood vessels) in patients undergoing liver surgery for cancer treatment.

The liver plays a key role in regulating the process of blood clotting. As a result, blood clots are a major cause of complications and death following liver surgery. This is especially true in cancer patients who are at a higher risk of developing blood clots. Current methods for preventing clotting complications after liver surgery include conventional coagulation blood tests (CCTs) and anticoagulant drugs, such as low molecular weight heparins (LMWHs). Current LMWH treatment is prescribed for one month after surgery, but studies show that the risk of developing blood clots can last up to 3 months. Studies also show that CCTs may not be as effective in detecting clotting issues as more comprehensive testing systems, such as TEG. This study will randomize 50 participants to receive 90 days of thromboprophylaxis (using the LMWH Redesca) or the standard of care 30 days (using the LMWH Fragmin) after liver surgery. The medication will be given by injection, similar to a regular vaccine or an insulin injection. Participants will inject the medication every day, for 30 or 90 days, after surgery. Participants will also have their blood tested for clotting issues via TEG testing before surgery and on post-operative days 1,3,5,30 and 90. After surgery, participants will be monitored by their surgeon for clotting complications and 3 year disease-free survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Thrombosis; Hepatic Disease; Surgery-Complications; Hypercoagulability
• Intervention / Treatment: Drug: Redesca (enoxaparin sodium for injection); Drug: Fragmin (dalteparin)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Crystal Engelage, PhD; Phone Number: 37517 519-685-8500; Email: Crystal.Engelage@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged 18 years or older at the time of enrollment.
2. Requiring major liver resection (>2 liver sections) for any oncologic indication.
3. Requiring postoperative thromboprophylaxis will be included.
4. Willing and able to perform subcutaneous injections according to the study protocol, or receive injections form a caregiver delegated by the participant.

Exclusion Criteria:

1. Anyone below 18 years of age.
2. Patients on current anticoagulant and/or antiplatelet therapy
3. Patients with a history of thrombotic events
4. Patients with a coagulation disorder.
5. Patients with recognized thrombophilia.
6. Patients who cannot understand/speak or read in English.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Redesca; Patients in the extended thromboprophylaxis group will receive Redesca (enoxaparin sodium for injection) (40mg) once a day, starting on the day of surgery, for 90 days postoperatively.	Drug: Redesca (enoxaparin sodium for injection); Redesca is low molecular weight heparin and a biosimilar biologic drug (biosimilar) to Lovenox. Indications have been granted on the basis of similarity between Redesca and the reference biologic drug Lovenox. As such, Redesca (enoxaparin sodium) is indicated for thromboprophylaxis in patients undergoing high risk abdominal and colorectal surgeries. Doses are provided as self-administered subcutaneous injections using a pre-filled syringe with a protective shield.
Active Comparator: Fragmin; Patients in the standard of care group will receive Fragmin (daletparin) (5,000 I.U) once a day, starting on the day or surgery, for 30 days postoperatively.	Drug: Fragmin (dalteparin); Fragmin is a low molecular weight heparin indicated for thromboprophylaxis in patients undergoing high risk abdominal and colorectal surgeries. Doses are provided as self-administered subcutaneous injections using a pre-filled syringe with a protective shield. Our institution uses this drug for standard of care thromboprophylaxis (30 days) in this patient population.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number pf participants with hypercoagulability identified via TEG testing	All participants will have postoperative TEG testing performed for the detection of hypercoagulability.	Preoperatively (with pre-admission blood work) through to 90 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombotic Events	Determining the occurrence of postoperative venous thrombotic events between treatment groups	Up to 6 months postoperatively
Disease Free Survival	Comparing disease free survival (DFS) rates between treatment groups	Up to 3 years postoperatively

Collaborators and Investigators

• Sponsor: Western University, Canada
• Collaborators: Valeo Pharma Inc
• Investigators: Principal Investigator: Anton Skaro, MD PhD, Western Univeristy/LHSC

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 22, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Embolism and Thrombosis; Liver Diseases; Thrombosis; Thrombophilia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Enoxaparin sodium
• Other Study ID Numbers: 123658

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not planning to share IPD with other researchers

Drug and device information, study documents

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