Pre- vs Postoperative Thromboprophylaxis for Liver Resection (PREPOSTEROUS)

Pre- vs Postoperative Thromboprophylaxis for Liver Resection - a Prospective, Multicenter, Randomized Controlled Trial

Thromboprophylaxis for liver surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in liver surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing liver surgery. As far as we know, there are no prospective randomized trials in this field, and current guidelines are unfortunately based on very low quality evidence, that is, a few retrospective studies and expert opinion. Both American and European thromboprophylaxis guidelines for abdominal cancer surgery support the preoperative initiation of thromboprophylaxis, but these guidelines do not specifically address the increased bleeding risk associated with liver surgery. On the contrary, Dutch guidelines recommend postoperative thromboprophylaxis only, because of lack of evidence for preoperative thromboprophylaxis. Traditionally, many liver surgery units have been reluctant in using preoperative thromboprophylaxis due to the potentially increased risk of bleeding complications. Enhanced Recovery After Surgery (ERAS) Society Guidelines recommend preoperative thromboprophylaxis in liver surgery, but the guidelines provide no supporting evidence for this recommendation. Overall, the amount of evidence is scarce and somewhat contradictory in this clinically relevant field of thromboprophylaxis in liver surgery. The aim of this study is to compare pre- and postoperatively initiated thromboprophylaxis regimens in liver surgery in a randomized controlled trial.

Study Overview

• Status: Recruiting
• Conditions: Bleeding; Surgery; Liver Cancer; Embolism, Pulmonary; Thrombosis, Deep Vein
• Intervention / Treatment: Drug: enoxaparin or tinzaparin or dalteparin; Drug: No intervention

• Study Type: Interventional
• Enrollment (Anticipated): 1012
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ville Sallinen, MD, PhD; Phone Number: +358-9-4711; Email: ville.sallinen@helsinki.fi

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Hospital
    • Contact: Aki Uutela, MD; Phone Number: +358-9-4711; Email: aki.uutela@hus.fi
  • Kuopio, Finland
    • Recruiting
    • Kuopio University Hospital
    • Contact: Pekka Lammi, MD; Email: pekka.lammi@kys.fi
  • Oulu, Finland
    • Not yet recruiting
    • Oulu University Hospital
    • Contact: Heikki Karjula, MD, PhD; Email: heikki.karjula@ppshp.fi
  • Tampere, Finland
    • Recruiting
    • Tampere University Hospital
    • Contact: Yrjö Vaalavuo, MD; Email: yrjo.vaalavuo@pshp.fi
  • Turku, Finland
    • Not yet recruiting
    • Turku University Hospital
    • Contact: Maija Lavonius, MD; Email: maija.lavonius@tyks.fi
• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Sheraz Yaqib, MD; Email: shya@ous-hf.no

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:

• All patients undergoing liver resection

Exclusion Criteria:

• Patient on anticoagulative medication (heparin, low-molecular weight heparin, warfarin, direct oral anticoagulants) during last month pre-surgery
• Emergency operation (e.g. for trauma or infection)
• Age < 18 years
• Allergy or other contraindication to planned low-molecular weight heparin
• Inability to give written informed consent
• Liver resection not performed (removed from analyses after randomization)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative thromboprophylaxis; Preoperatively initiated tromboprophylaxis	Drug: enoxaparin or tinzaparin or dalteparin; Thromboprophylaxis initiated approximately 14 hours prior to the planned liver resection skin incision. Thromboprophylaxis can be initiated using enoxaparin (20 - 40 mg), tinzaparin (2500 - 4500 IU), or dalteparin (2500 - 5000 IU), with the dose based on patient's renal function
Other: Postoperative thromboprophylaxis; Postoperatively initiated thromboprophylaxis	Drug: No intervention; No preoperative thromboprophylaxis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous thromboembolisms	Number of patients with venous thromboembolism defined as either 1) symptomatic deep venous thromboembolism (includes all deep veins e.g. all extremities, portal vein, and superior mesenteric) diagnosed using ultrasound or computed tomography or magnetic resonance imaging, or in re-laparatomy/surgery, 2) pulmonary embolism diagnosed using computed tomography, magnetic resonance imaging, or lung perfusion imaging, or 3) death due to venous thromboembolism	within 30 days from liver resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Posthepatectomy haemorrhage	Number of patients with posthepatectomy haemorrhage, any grade in ISGLS classification	within 30 days from liver resection
Postoperative complications	Comprehensive Complication Index - score	within 30 days from liver resection
Length of postoperative hospital stay	Length of postoperative hospital stay, days	within 30 days from liver resection
Blood transfusion	Total amount of transfused red blood cells, units	during and within 30 days from liver resection

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: Academy of Finland; The Finnish Medical Association

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: HYKS-PREPOSTEROUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No