Pre- vs. Postoperative Thromboprophylaxis in Pancreatic Surgery

Study Overview
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Brief Summary
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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.

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

Conditions
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Pancreas Cancer, Pancreas Neoplasm, Surgery, Thrombosis, Bleeding

Intervention / Treatment
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* Drug: enoxaparin/tinzaparin/dalteparin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preoperative thromboprophylaxis<br>Preoperatively initiated tromboprophylaxis | Drug: enoxaparin/tinzaparin/dalteparin<br>* 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).<br>|
| No Intervention: Postoperative thromboprophylaxis<br>Postoperatively initiated thromboprophylaxis | |

What is the study measuring?
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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 |