Tisseel® as a Reinforcement of Esophagojejunal Anastomoses

July 21, 2020 updated by: Elisenda Garsot Savall, Germans Trias i Pujol Hospital

The Use of Fibrin Glue Sealant (Tisseel®) as a Reinforcement of Esophagojejunal Anastomoses Will Decrease the Rate of Anastomotic Leak.

Background:

The dehiscence of esophagojejunal anastomoses is one of the most serious complications after total gastrectomy in patients with gastric cancer. Any method of avoiding this problem will affect not only the postoperative course but also the prognostic of disease.

Methods:

This is a prospective, randomized and multicenter trial, within the Spanish EURECCA Esophagogastric Cancer Group, to investigate the efficacy of Tisseel® in reducing the rate of esophagojejunal anastomosis leakage in patients with gastric cancer. The rate of anastomosis leak will be measured with clinical, radiological and analytic parameters.

Objective:

Analyze the efficacy of Tisseel® as a reinforcement in reducing the rate of anastomotic esophagojejunal anastomoses.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Introduction The dehiscence of the esophagojejunal anastomosis is one of the most serious complications after a total gastrectomy not only in the short term but it has been shown to be an independent risk factor for survival. The rate of esophagojejunal anastomosis leakage after cancer gastrectomies is described to be between 1-12.3%.

Any method to prevent this complication would be of vital importance to improve the evolution of these patients. Likewise, when the dehiscence has been established, early detection could contribute to an early intervention, avoiding more serious consequences and, therefore, improving the short and long term prognosis.

Little progress has been made during recent decades in the prevention of anastomotic leakage in high-risk digestive tract anastomosis. Some authors have tried the use of new methods of suture, reinforcements or patches in the anastomosis. Fibrin adhesives were introduced more than 30 years ago, in order to favor hemostasis and tissue adhesion. Numerous studies have demonstrated their effectiveness in reducing surgical bleeding in cardiovascular surgery but its role as a sealant in gastrointestinal anastomosis is more debated. There have been some experimental studies that have shown a possible protective effect of this material in enteric anastomoses. With the evolution of bariatric surgery and with the high volume of surgeries handled, several studies have been published that assess the effect of fibrin sealants on gastrojejunal anastomoses. In esophagogastric surgery, the number of published studies is reduced and there are only 2 studies that assess the effect of fibrin sealants on esophagojejunal anastomosis. The results of these studies seem to indicate that the application of fibrin sealants in this anastomosis could have a favorable effect in reducing the number of anastomotic dehiscences.

There are different definitions for the concept of "anastomotic dehiscence". The dehiscence of the esophago-jejunal anastomotic can be defined as any clinical and / or radiological evidence of dehiscence of the anastomosis. Although early diagnosis is key to avoiding major consequences, in clinical practice, the diagnosis of anastomotic dehiscence is often delayed. Direct observation of the debit of surgical drainage, fever or persistent ileus or clear symptoms of peritonitis are indirect signs that make us suspect a possible anastomotic dehiscence. The possibility of having a parameter that allows us to diagnose early a problem in the suture would allow us to act earlier and, therefore, improve the prognosis of these patients in the short and long term.

In colorectal surgery, serological parameters such as procalcitonin or C-reactive protein have been studied as early predictors of anastomotic dehiscence. In esophagogastric surgery, publications are scarce and all of them analyze results in esophagogastric anastomoses.

Furthermore, the determination of amylases in drainage has also been used for the detection of postoperative fistula. It is a simple and low cost method and is a parameter widely used in pancreatic surgery for the detection and evolutionary control of pancreatic fistulas. It has also been shown to be useful in esophageal surgery and in bariatric surgery. However, in gastric cancer it has only been used for the diagnosis of pancreatic fistula as a complication in total gastrectomies with associated splenectomy.

Finally, the use of radiology with oral contrast routinely in the postoperative period of esophagogastric surgery has been shown to have a low sensitivity for the early detection of anastomotic dehiscence. CT with oral contrast seems to have greater sensitivity and positive predictive value in esophageal surgery for this purpose, but the need to perform a postoperative test to evaluate the anastomosis without clinical evidence of dehiscence is unclear.

For all these reasons, we believe that a multicenter randomized study will contribute to improve the clinical results of esophagogastric surgery and the knowledge of the diagnosis of complications, by studying the efficacy of Tisseel® in reducing the rate of anastomotic leakage, but also analyzing the role of drain amylases, serum CRP (C-reactive protein), procalcitonin and white blood cell levels in the early detection and prediction of anastomotic leak, and the role of CT with oral contrast as a routine assessment of anastomotic integrity.

Objective Analyze the efficacy of Tisseel® in reducing the rate of anastomotic leakage diagnosed in the postoperative period using clinical and / or radiological parameters.

Methods This is a prospective, randomized and multicenter trial, within the Spanish EURECCA Esophagogastric Cancer Project, to investigate the efficacy of Tisseel® in reducing the rate of esophagojejunal anastomosis leakage in patients with gastric cancer.

Participation study will be offered to all centers that are currently part of the Spanish EURECCA Esophagogastric Cancer Group. Those hospitals that show their desire to participate must sign the Letter of Commitment. In the same way, the study must sign off by European Medicine Agency and Spanish Agency of Medicines.

Once the patient is included in the study the surgeon performs a total gastrectomy as usual procedure. Once the esophagojejunal anastomosis is done the patient is randomized (Tisseel® vs no product). Surgeon dispenses Tisseel® all over the anastomosis following data sheet if applicable. The rest of the surgical procedure is as usual. In the postoperative period the investigator collects the data commented in following sections.

The evidence of an anastomotic leak will be tested with analytical and radiological parameters:

  1. Blood samples will be taken from patients at:

    • Immediate preoperative (blood count, procalcitonin and C-reactive protein)
    • Days 1, 3, 5 and 7 postoperative (blood count, procalcitonin and C-reactive protein).
  2. A sample of surgical drainage will be collected for the determination of amylases on days: 1,3,5, and 7 postoperative or until drainage is withdrawn.
  3. An abdominal CT with oral contrast will be performed within the first 5 postoperative days. The date and the result will be collected.

Study Type

Interventional

Enrollment (Anticipated)

146

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Badalona, Barcelona, Spain, 08016
        • Recruiting
        • Elisenda Garsot Savall
        • Contact:
        • Sub-Investigator:
          • Sara Sentí, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients over 18 years diagnosed with gastric adenocarcinoma and scheduled for a total gastrectomy with curative intent in EURECCA Esophagogastric Cancer Group who agree to participate in the study and sign the informed consent

Exclusion Criteria:

  • Patients with non-epithelial neoplasms, with metastases, not resected or undergoing palliative resections. Patients who do not sign informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tisseel®
Once the esophagojejunal anastomosis is done the patient is randomized (Tisseel® vs no product). In the arm "Tisseel®" surgeon dispenses the product all over the anastomosis. The rest of the surgical procedure is as usual.
Drug: Tisseel
Reinforcement of esophagojejunal anastomoses after total gastrectomy with the product.
Other: no Tisseel®
Once the esophagojejunal anastomosis is done the patient is randomized (Tisseel® vs no product). In the arm " noTisseel®" surgeon performs the surgical procedure as usual.
Device: No Tisseel
No reinforcement of esophagojejunal anastomoses after total gastrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of esophagojejunal anastomotic leak in immediate postoperative period
Time Frame: 7 days
Clinical or radiological (see anex 1: Score Goense) evidence of esophagojejunal anastomotic leak.
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amylases level in drainage
Time Frame: days 1,3,5,7 postoperatively
Amylase level (mg/L) in drainage
days 1,3,5,7 postoperatively
CRP (C-reactive protein) in blood
Time Frame: days 1,3,5,7 postoperatively
C-reactive protein in blood (mg/L)
days 1,3,5,7 postoperatively
Procalcitonin in blood
Time Frame: days 1,3,5,7 postoperatively
Procalcitonin in blood (mg/L)
days 1,3,5,7 postoperatively
White cell levels in blood
Time Frame: days 1,3,5,7 postoperatively
White cell levels in blood (x109/L)
days 1,3,5,7 postoperatively
Results of Computed Tomography with oral contrast.
Time Frame: between 3th and 5th postoperative day

The results will be expressed based on Goense Score

Based on Score Goense (Anastomotic Leakage Prediction Score). The investigator will collect the presence of:

Yes No Normal Fluid collection Air cavity Fistula Wall discontinuity Empiema

Goense L, Stassen PMC, Wessels FJ, van Rossum PSN, Ruurdal JP, van Leeuwen MS, van Hillegersberg R. Diagnostic performance of a CT-based scoring system for diagnosis of anastomotic leakage after esophagectomy: comparison with subjective CT assessment. Eur Radiol 2017; 27:4426-34
between 3th and 5th postoperative day
Type of esophagojejunal anastomoses performed
Time Frame: day of intervention

The type of esophagojejunal anastomoses performed can be:

  1. mechanical (circular)
  2. mechanical (lineal)
  3. manual
day of intervention
Postoperative complications
Time Frame: 30 days after surgery

Postoperative complications (Clavien-Dindo score):

Grade I Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions

Grade II Requiring pharmacological treatment with drugs other than such allowed for grade I complications.

Grade III Requiring surgical, endoscopic or radiological intervention

  • IIIa Intervention not under general anesthesia
  • IIIb Intervention under general anesthesia

Grade IV Life-threatening complication requiring IC/ICU-management

  • IVa single organ dysfunction (including dialysis)
  • IVb multiorgandysfunction

Grade V Death of a patient
30 days after surgery
90-day mortality
Time Frame: 90 days after surgery
Mortality at 90 days after surgery
90 days after surgery
Need for urgent surgical re-intervention
Time Frame: 30 days after surgery

Reintervention after surgery:

Yes/Not
30 days after surgery
Hospital stay
Time Frame: 30 days after surgery
Number of days of hospital stay
30 days after surgery
Readmission
Time Frame: 30 days after discharge

Readmission within 30 days after discharge:

Yes/Not
30 days after discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Germans Trias i Pujol Hospital

Investigators

  • Principal Investigator: Elisenda Garsot, Germans Trias i Pujol Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2020

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

July 1, 2022

Study Registration Dates

First Submitted

October 18, 2018

First Submitted That Met QC Criteria

November 5, 2018

First Posted (Actual)

November 7, 2018

Study Record Updates

Last Update Posted (Actual)

July 23, 2020

Last Update Submitted That Met QC Criteria

July 21, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Tisseel

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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