OBSiDiAN in a Stapled Circular Esophagogastric Anastomosis After Ivor Lewis Esophagectomy

• ClinicalTrials.gov Identifier: NCT05713955
• Recruitment Status: Withdrawn
• First Posted: February 6, 2023
• Last Update Posted: January 12, 2024
• Sponsor: University Hospital, Ghent
• Information provided by (Responsible Party): University Hospital, Ghent

Tracking Information

• First Submitted Date: November 8, 2021
• First Posted Date: February 6, 2023
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: January 9, 2024
• Estimated Primary Completion Date: July 1, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2023)

Anastomotic leak [ Time Frame: Absence of anastomotic leak within 30 days post operatively ]

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

Original Primary Outcome Measures (submitted: February 1, 2023)

Anastomotic leak [ Time Frame: Absence of anastomotic leak within 30 days post operatively ]

Anastomotic leak defined according to the ECCG guidelines11 type III: localized defect requiring surgical therapy

Current Secondary Outcome Measures (submitted: May 25, 2023)

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

Original Secondary Outcome Measures (submitted: February 1, 2023)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: OBSiDiAN in a Stapled Circular Esophagogastric Anastomosis After Ivor Lewis Esophagectomy
• Official Title: 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.
• Brief Summary: Multicentre randomized controlled trial to evaluate the effectiveness of an autologous BioMatrix on a circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy.

Detailed Description

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).

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant)
Masking Description:

Eligible patients will be randomized in a 1:1 allocation to either the autologous BioMatrix OBSiDiAN group (study group) or the standard of care group (control group). Subjects will be randomized at the ending of the abdominal phase of the surgery. In the event, that a potential subject fails the intra-operative criteria, an intention-to-treat protocol is followed. Given the nature of the study, blinding the surgeon to the treatment is not possible. The patient will be blinded for the study.

Primary Purpose: Treatment

• Condition: Anastomotic Leak Esophagus

Intervention

Device: Obsidian

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

Study Arms

• Active Comparator: study group
  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.
  Intervention: Device: Obsidian
• No Intervention: standard group
  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.

• Publications *: Plat VD, Bootsma BT, van der Wielen N, van der Peet DL, Daams F. Autologous Activated Fibrin Sealant for the Esophageal Anastomosis: A Feasibility Study. J Surg Res. 2019 Feb;234:49-53. doi: 10.1016/j.jss.2018.08.049. Epub 2018 Sep 27.

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: January 9, 2024): 0
• Original Estimated Enrollment (submitted: February 1, 2023): 250
• Estimated Study Completion Date: July 1, 2028
• Estimated Primary Completion Date: July 1, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05713955
• Other Study ID Numbers: BC-09974
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital, Ghent
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Ghent
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Piet Pattyn; UZ Gent

• PRS Account: University Hospital, Ghent
• Verification Date: January 2024