PREPOSTEROUS2: Pre- vs. Postoperative Thromboprophylaxis in Pancreatic Surgery

Sponsor

Helsinki University Central Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05245877

Collaborator

(none)

800

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreas Cancer Pancreas Neoplasm Surgery Thrombosis Bleeding	Drug: enoxaparin/tinzaparin/dalteparin	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Venous thromboembolism, number of patients [within 30 days from pancreatic resection]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients undergoing either

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

Exclusion Criteria:

Patient on anticoagulative medication (heparin, low-molecular weight heparin, warfarin, direct oral anticoagulants) during the month (30 days) preceding surgery
Emergency operation (e.g. for trauma, infection or pancreatitis)
Age < 18 years
Allergy or other contraindication to planned low-molecular weight heparin
Inability to give written informed consent
Pancreatic resection not performed (removed from analyses after randomization)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Helsinki University Central Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ville Sallinen, Primary investigator, Helsinki University Central Hospital

ClinicalTrials.gov Identifier:

NCT05245877

Other Study ID Numbers:

HYKS-PREPOSTEROUS2

First Posted:

Feb 18, 2022

Last Update Posted:

Feb 18, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Heparin, Low-Molecular-Weight

Study Results

No Results Posted as of Feb 18, 2022