OBSiDiAN in a Stapled Circular Esophagogastric Anastomosis After Ivor Lewis Esophagectomy

Study Overview
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Brief Summary
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Multicentre randomized controlled trial to evaluate the effectiveness of an autologous BioMatrix on a circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy.

Detailed Description
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STUDY PRODUCT Autologous BioMatrix: Obsidian (medical device class III) STUDY POPULATION Subjects ≥ 18 years and ≤ 75 years of age scheduled for elective Ivor Lewis esophagectomy for oesophageal cancer with a circular stapled intrathoracic esophagogastric anastomosis. SAMPLE SIZE A total of 600 patients will be included in the study. 300 patients in each study arm. ENROLEMENT PERIOD Based on an annual number of 70-80 esophagectomies in this centre, University Hospital Ghent, with inclusion of patients in other European high volume centers, we predict an enrolment period of 4 years. PRIMARY ENDPOINT Anastomotic leak type I, II and III within 30 days post operatively. Anastomotic leak is defined according to the Esophagectomy Complications Consensus Group (ECCG).

Official Title
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Evaluation of Effectiveness and Safety of Autologous BioMatrix OBSiDiAN to Enhance a Stapled Circular Esophagogastric Anastomosis After Ivor Lewis Esophagectomy in a Multicentre Randomized Controlled Trial.

Conditions
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Anastomotic Leak Esophagus

Intervention / Treatment
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* Device: Obsidian


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: preoperatively Subjects ≥ 18 years and ≤ 75 years who are willing to participate and provide written informed consent prior to any study-related procedures. Subjects with oesophageal carcinoma scheduled for elective minimally invasive or open Ivor Lewis esophagectomy Intra-operatively intrathoracic circular stapled esophagogastric anastomosis Exclusion Criteria: preoperatively Female patients who are pregnant or nursing Participation in another study involving investigational drugs or devices. Use of Avastin within 30 days prior to surgery ASA IV (American Society of Anesthesiologists physical status classification system: patient with severe systemic disease that is a constant threat to life) Patients with other malignancies Patients with previous esophageal or gastric surgery Known hypersensitivity to batroxobin and tranexamic acid. Hemoglobin level < 8 g/dL Patients on medicine containing acetylsalicylic acid not able to stop using the medicine for medical reasons 3 days before taking the blood sampling. Patients on clopidogrel not able to stop clopidogrel for medical reasons 7 days before blood sampling Patients on other platelet aggregation inhibitor therapies not able to stop using the platelet aggregation inhibitor therapies for 3 days before taking the blood sample. Intra-operatively Intra-operative findings that may preclude conduct of the study procedures, such as pleural metastasis, tumor invasion in other organs, … Anastomosis preformed differently than the standard of care Excessive bleeding (>500 ml) prior to anastomosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Design : An international, multicentre randomized controlled trial evaluating the effectiveness and safety of autologous BioMatrix OBSiDiAN in reducing the incidence of anastomotic leaks following Ivor Lewis esophagectomy for oesophageal carcinoma. Randomization : Eligible patients will randomized in a 1:1 allocation to either the autologous BioMatrix OBSiDiAN group (study group) or the standard of care group (control group). Procedure: For both the control group and intervention group: A standard laparoscopic, robotic or open Ivor Lewis esophagectomy with an intrathoracic end-to-side stapled esophagogastric anastomosis. For the intervention group: After the abdominal fase and randomisation, a 120 ml blood sample will be drawn from the patient and put in the Vivostat® processor unit to make Obsidian. At the time of the anastomosis Obsidian will be applied between and around the esophagogastric anastomosis
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: study group<br>For the study group, a unit of autologous BioMatrix OBSiDiAN will be produced. Blood sample (120ml) will be taken after randomization at the ending of the abdominal phase of the surgery. The surgeon will create an esophagogastric anastomosis, after ruling out tension or torsion. Around 1-2ml of autologous BioMatrix OBSiDiAN will be applied on the distal/or proximal resection stump before the stapled anastomose will be created. After firing the standard circular device and creation of a functional anastomosis, a further 2.5-3ml OBSiDiAN must be applied circumferentially on the outside on the anastomosis. Once application is completed, a 30 seconds waiting period is required before putting the esophagus back into the surgical field (study specific). A methylene blue leakage test or other leakage test is performed (standard of care). If there is a leak, the anastomosis will be corrected or the completed procedure has to be done again. | Device: Obsidian<br>* To create OBSiDiAN BioMatrix, 120 ml of the the patient's blood is added to the processing unit. The Vivostat® processor unit heats, separates, centrifugates to get the plasma. Batroxobin is added. After again processing, the result is an OBSiDian syringe filled with BioMatrix Obsidian®ASG. This will be applied on the anastomosis<br>|
| No Intervention: standard group<br>The surgeon will create an esophagogastric anastomosis, after ruling out tension or torsion. A methylene blue leakage test or other leakage test is performed (standard of care). If there is a leak, the anastomosis will be corrected. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anastomotic leak | Anastomotic leak defined according to the ECCG guidelines type I: local defect requiring no change in therapy or treated medicallly or with dietary modifications type II: localized defect requiring interventional but not surgical therapy, for example, interventional radiology drain, stent or bedside opening and packing or incision type III: localized defect requiring surgical therapy | Absence of anastomotic leak within 30 days post operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | in hospital mortality | from surgery until 30 days post operative | 
| sepsis | in hospital sepsis | from surgery until 30 day post operative | 
| pneumonia | in hospital pneumonia | from surgery until 30 day post operative | 
| late anastomotic leakage | late anastomotic leakage (ECCG type I, II and III) | from surgery until 90 days post operative | 
| stricture | stricture of the esophagogastric anastomosis | from surgery until 1 year post operative | 
| inflammation WBC | post operative inflammation (WBC) | from date of randomisation to postoperative day 5 | 
| inflammation CRP | post operative inflammation (CRP) | from date of randomisation to postoperative day 5 | 
| ICU stay | length of ICU stay | from surgery until discharge or until the date of death from any cause, whichever came first, assessed up to 3 months | 
| hospital stay | total hospital stay | from surgery until discharge or until the date of death from any cause, whichever came first, assessed up to 3 months | 
| thoracic drainage volume | Volume of thoracic drain | from surgery until removal of thoracic drain within the first week postoperative | 
| thoracic drainage duration | duration of thoracic drain | from surgery until removal of thoracic drain within the first week postoperative |