Clinical trial NCT03733639: Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
Official title: The Use of Fibrin Glue Sealant (Tisseel®) as a Reinforcement of Esophagojejunal Anastomoses Will Decrease the Rate of Anastomotic Leak.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Gastric Cancer
Anastomotic Leak
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2018-11-07
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of esophagojejunal anastomotic leak in immediate postoperative period
timeFrame: 7 days
Secondary outcomes:
measure: Amylases level in drainage
timeFrame: days 1,3,5,7 postoperatively
measure: CRP (C-reactive protein) in blood
timeFrame: days 1,3,5,7 postoperatively
measure: Procalcitonin in blood
timeFrame: days 1,3,5,7 postoperatively
measure: White cell levels in blood
timeFrame: days 1,3,5,7 postoperatively
measure: Results of Computed Tomography with oral contrast.
timeFrame: between 3th and 5th postoperative day
measure: Type of esophagojejunal anastomoses performed
timeFrame: day of intervention
measure: Postoperative complications
timeFrame: 30 days after surgery
measure: 90-day mortality
timeFrame: 90 days after surgery
measure: Need for urgent surgical re-intervention
timeFrame: 30 days after surgery
measure: Hospital stay
timeFrame: 30 days after surgery
measure: Readmission
timeFrame: 30 days after discharge
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Elisenda Garsot Savall
state: Barcelona
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Elisenda Garsot
role: PRINCIPAL_INVESTIGATOR
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