Pre- Vs Postoperative Thromboprophylaxis for Liver Resection

NCT04731558 | Recruiting Phase 4

• 1 other identifier: HYKS-PREPOSTEROUS
• Study Type: interventional
• Target: 1,012
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Liver Cancer; Surgery; Thrombosis, Deep Vein; Embolism, Pulmonary; Bleeding

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Posthepatectomy haemorrhage

  within 30 days from liver resection

• Postoperative complications

  within 30 days from liver resection

• Length of postoperative hospital stay

  within 30 days from liver resection

• Blood transfusion

  during and within 30 days from liver resection

Study Arms (2)

Preoperative thromboprophylaxis

EXPERIMENTAL

Preoperatively initiated tromboprophylaxis

Drug: enoxaparin or tinzaparin or dalteparin

Postoperative thromboprophylaxis

OTHER

Postoperatively initiated thromboprophylaxis

Drug: No intervention

Interventions

enoxaparin or tinzaparin or dalteparin DRUG

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

Preoperative thromboprophylaxis

No intervention DRUG

No preoperative thromboprophylaxis.

Postoperative thromboprophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients undergoing liver resection

You may not qualify if:

• 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)

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Academy of Finland: collaborator
• The Finnish Medical Association: collaborator

Study Sites (7)

Helsinki University Hospital

Helsinki, Finland

RECRUITING

Kuopio University Hospital

Kuopio, Finland

RECRUITING

Oulu University Hospital

Oulu, Finland

NOT YET RECRUITING

Tampere University Hospital

Tampere, Finland

RECRUITING

Turku University Hospital

Turku, Finland

NOT YET RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

University Hospital of North Norway

Tromsø, Norway

RECRUITING

MeSH Terms

Conditions

Liver Neoplasms; Venous Thrombosis; Pulmonary Embolism; Hemorrhage

Interventions

Enoxaparin; Tinzaparin; Dalteparin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Central Study Contacts

Ville Sallinen, MD, PhD

CONTACT

+358-9-4711; ville.sallinen@helsinki.fi

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 1, 2021
• Study Start: February 10, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 14, 2025

Record last verified: 2025-02

Locations

FI (5); NO (2)