Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery (PREPOSTEROUS2)

Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery - a Prospective, Multicenter, Randomized Controlled Trial (PREPOSTEROUS Pancreas Trial)

Thromboprophylaxis for pancreatic surgery can be commenced either preoperatively or postoperatively. Despite a clear trade-off between thrombosis and bleeding in pancreatic surgery patients, there is no international consensus when thrombosis prophylaxis should be commenced in patients undergoing pancreatic surgery. 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 pancreatic surgery. On the contrary, Dutch guidelines recommend postoperative thromboprophylaxis only, because of lack of evidence for preoperative thromboprophylaxis. Enhanced Recovery After Surgery (ERAS) Society Guidelines recommend preoperative thromboprophylaxis in pancreatic 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 pancreatic surgery. The aim of this study is to compare pre- and postoperatively initiated thromboprophylaxis regimens in pancreatic surgery in a randomized controlled trial.

Study Overview

• Status: Recruiting
• Conditions: Thrombosis; Bleeding; Surgery; Pancreas Cancer; Pancreas Neoplasm
• Intervention / Treatment: Drug: enoxaparin/tinzaparin/dalteparin

• Study Type: Interventional
• Enrollment (Estimated): 800
• 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

• Canada
  • Toronto, Canada
    • Recruiting
    • Sunnybrook Health Sciences Centre
    • Contact: Paul Karanicolas; Phone Number: 416-480-6100; Email: paul.karanicolas@sunnybrook.ca
• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Hospital
    • Contact: Tea Kontio, MD,PhD; Email: tea.kontio@hus.fi
  • Oulu, Finland
    • Recruiting
    • Oulu University Hospital
    • Contact: Minna Nortunen, MD, PhD; Phone Number: +358 8 3152011; Email: minna.nortunen@ppshp.fi
  • Tampere, Finland
    • Recruiting
    • Tampere University Hospital
    • Contact: Johanna Laukkarinen, MD, PhD, Professor; Phone Number: +358 3 311 61; Email: johanna.laukkarinen@pirha.fi
• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Knut J Labori, MD, PhD, Professor; Phone Number: +47 22 11 80 80; Email: uxknab@ous-hf.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All patients undergoing either

1. pancreaticoduodenectomy or total pancreatectomy (for any indication) or
2. distal pancreatectomy for suspicion of cancer

Exclusion Criteria:

1. Patient on anticoagulative medication (heparin, low-molecular weight heparin, warfarin, direct oral anticoagulants) during the month (30 days) preceding surgery
2. Emergency operation (e.g. for trauma, infection or pancreatitis)
3. Age < 18 years
4. Allergy or other contraindication to planned low-molecular weight heparin
5. Inability to give written informed consent
6. Pancreatic 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/tinzaparin/dalteparin; Patients randomized to the preoperative thromboprophylaxis will have their thromboprophylaxis initiated approximately 2-14 hours prior to the planned pancreatic surgery skin incision (depending on the center's current practice and logistics). 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 according to the local standard of care. A center may reduce the dose 25-50% if the dose is given very close to the skin incision (i.e. at the morning of the operation instead of the evening before the operation).
No Intervention: Postoperative thromboprophylaxis; Postoperatively initiated thromboprophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous thromboembolism, number of patients	Number of patients that have venous thromboembolism, which include any of the following: 1) symptomatic deep venous thromboembolism (including all deep veins e.g. all extremities, portal-, and superior mesenteric vein) diagnosed using ultrasound or computed tomography or magnetic resonance imaging, or in re-laparotomy/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 pancreatic resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postpancreatectomy hemorrhage (PPH)	Postpancreatectomy hemorrhage (PPH), any grade in ISGPS classification for postpancreatectomy hemorrhage, number of patients	within 30 days from pancreatic resection
Comprehensive Complication Index - score	Comprehensive Complication Index - score	within 30 days from pancreatic resection
Length of postoperative hospital stay,	Length of postoperative hospital stay, days, within 30 days from pancreas resection including hospital stay due to readmission(s)	within 30 days from pancreatic resection
Transfused red blood cells	Total amount of transfused red blood cells, units, during and within 30 days from pancreas resection	during and within 30 days from pancreas resection
Post-operative hemoglobin below 70 g/l	Number of patients with post-operative hemoglobin below 70 g/l	during and within 30 days from pancreas resection

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Embolism and Thrombosis; Thrombosis; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Tinzaparin; Enoxaparin; Heparin, Low-Molecular-Weight; Dalteparin
• Other Study ID Numbers: HYKS-PREPOSTEROUS2

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
• product manufactured in and exported from the U.S.: No