Safety and Performance of a Synthetic Tissue Sealant in Reducing Fluid Leakage in Hepatobiliary and Pancreatic Surgery

Study Overview
=================
Brief Summary
-----------------
Polyganics BV (Groningen, The Netherlands), in close collaboration with University Hospital-Eppendorf (UKE) Hamburg, has developed the Sealing Device for use in hepato-pancreato-bilary (HPB) surgery to reduce leakage of fluids from the site of surgery into the abdominal cavity and as an adjunctive hemostatic device to control minimal to moderate bleeding at the surgical site. The Sealing Device has been challenged in pre-clinical testing (laboratory and in-vivo work), but has not been evaluated for safety and performance in humans. This investigation will be conducted to clinically assess the safety and performance of Sealing Device as a means to reduce bile and pancreatic juice leakage in hepato-pancreato-bilary (HPB) surgery. Secondarily, the control of minimal to moderate bleeding will be assessed. To achieve adequate representation of the primary objective, the study will contain two separate surgical patient groups: Liver and Pancreas. The primary objective of the study is to demonstrate safety and performance in reducing intra- and post-operative leakage (bile and pancreatic juices) by using the Sealing Device in patients undergoing elective hepatic resection or distal pancreatectomy. The study will be conducted as an open-label, single-arm, multicenter study with a 16 months follow up. Up to 80 patients (40 liver and 40 pancreas patients) will be enrolled at up to 7 sites in Europe.

Official Title
-----------------
Prospective, Multicenter Study to Evaluate the Safety and Performance of a syntHetic Tissue Sealant in Reducing fluId lEakage Following Elective hepatobiLiary anD Pancreatic Surgery

Conditions
-----------------
Pancreatectomy, Hepatic Resection

Intervention / Treatment
-----------------
* Device: Sealing Device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Preoperative inclusion criteria: Subjects will be eligible according the following criteria: Subjects who are able to provide a written informed consent prior to participating in the clinical investigation. Subjects who are ≥ 18 years old. Subjects who are able to comply with the follow-up or other requirements. Subjects who are planned for an elective hepatic resection or distal pancreatectomy. During the surgery, the patients also need to comply with the intraoperative criteria. Intraoperative inclusion criteria: Subjects will be eligible according the following criteria: 1. Patch is applied manually (during open procedure, conversion procedure, or laparoscopic assisted procedure). Exclusion Criteria: Preoperative exclusion criteria Subjects who meet any of the following criteria will be excluded from participation: Female subjects who are pregnant and/or breastfeeding. Subjects with a known allergy to any of the components of the Sealing Device (Polyurethane (SDPU), 8-ArmPEG40k-SC (SDA), Disodium Hydrogen Phosphate (Na2HPO4) (BS) and DC-Green #6 (SDD)). Subject with bleeding disorders requiring anti-coagulation medication (except acetylsalicylic acid). Subjects who receive double-coagulation. Subjects who receive peritoneal dialysis. Subjects who previously required liver transplantation. Subjects with a presence of systemic infection. Subject who previously participated in this study, or in any investigational drug- or device study within 30 days of screening. Subjects undergoing a procedure requiring an anastomosis (e.g. Klatskin tumours or Whipple). Intraoperative exclusion criteria: Subjects who meet any of the following criteria will be excluded from participation: Subjects with multivisceral resections, except resection of spleen. Not able to apply the patch(es) according to the Instructions For Use. Total surgery requiring > 3 HPB Sealing Devices of 10 x 5 cm (which equals a resection surface of more than 88cm2). Additional for liver group: Subjects with a Grade 3 or 4 of bleeding after primary closure after liver transection (Lewis 2016). Subjects with liver cirrhosis Grade C on the Child-Turcotte-Pugh score. Additional for pancreas group: Subjects with a margin of < 1 cm between the defect and the portal vein.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single-arm, multicenter study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sealing Device<br>Sealing Device applied in hepatic resection or distal pancreatectomy | Device: Sealing Device<br>* The Sealing Device is indicated for use in hepato-pancreato-biliary (HPB) surgery to reduce leakage of fluids from the site of surgery into the abdominal cavity and as an adjunctive hemostatic device to control minimal to moderate bleeding at the surgical site.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bile leakage | Incidence of post-operative bile leakage (International Study Group of Liver Surgery Bile leakage Grading Scale); categories in order of ascending severity: biochemical leak, Grade B or Grade C | 30 days | 
| Pancreatic leakage | Incidence of post-operative pancreatic juice leakage (International Study Group of Pancreas Surgery Grading Scale); categories in order of ascending severity: biochemical leak, Grade B or Grade C | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding | Intra-operative control bleeding | Day 1 | 
| Leak-associated comorbidities | Incidence of leak-associated comorbidities | 16 months | 
| re-intervention | Incidence of re-intervention | 16 months | 
| Ease of Use | Ease of Use of the device as measured by questionnaire | Day 1 | 
| Post-operative bile leakage | Incidence of post-operative bile leakage (liver only) | 90 and 180 days | 
| Post-hepatectomy haemorrhage (PHH) | Incidence of post-operative bleeding (liver only) | 30 days | 
| Post-operative pancreatic juice leakage | Incidence of post-operative pancreatic juice leakage (pancreas only) | 90 and 180 days | 
| Post-pancreatectomy haemorrhage (PPH) | Incidence of post-operative bleeding (pancreas only) | 30 days | 
| (Serious) Adverse Device Effects | Incidence of (Serious) Adverse Device Effects | 16 months | 
| Incidence of transfusion | Incidence of transfusion | 16 months | 
| Length of hospital stay | Length of hospital stay | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatic resection, Distal pancreatectomy, Sealant