Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas

Official title

Pancreaticojejunostomy With or Without Modified N-butyl-2-cyanoacrylate Following Pancreaticoduodenectomy in Soft Pancreas: Randomized Controlled Trial

Overview

This is a single-center, randomized controlled trial comparing the efficacy of pancreaticojejunostomy with modified N-butyl-2-cyanoacrylate(Glubran® 2) versus standard pancreaticojejunostomy without cyanoacrylate in preventing postoperative pancreatic fistula (POPF) in patients undergoing pancreaticoduodenectomy with soft pancreatic texture. The primary endpoint is the incidence of postoperative pancreatic fistula at 30 days post-surgery, as defined by the International Study Group on Pancreatic Fistula (ISGPF) criteria.Secondary outcomes include surgical complications and length of hospital stay. The study will enroll approximately 194 patients at a single center.

Detailed description

Postoperative pancreatic fistula (POPF) remains the most common and serious complication following pancreaticoduodenectomy, with incidence rates reaching up to 56.7% in patients with soft pancreatic texture. The soft pancreatic parenchyma is particularly vulnerable to anastomotic breakdown due to its friable nature and difficulty in achieving secure suturing.

N-butyl-2-cyanoacrylate is a biodegradable tissue adhesive that polymerizes rapidly upon contact with hydroxide ions in tissue fluids, forming a strong, flexible bond. The application of modified N-butyl-2-cyanoacrylate to pancreaticoenteric anastomoses may reduce the incidence of POPF by providing additional mechanical reinforcement and sealing of minor leaks.

This is a phase III, single-center, prospective, randomized controlled trial with parallel groups. Eligible patients will undergo intraoperative assessment of pancreatic texture (soft confirmed by surgeon's palpation). Randomization will occur intraoperatively after resection but before reconstruction, using computer-generated blocks.

This study aims to evaluate whether the application of modified N-butyl-2-cyanoacrylate (Glubran® 2) during pancreaticojejunostomy can significantly reduce the incidence of POPF in patients with soft pancreatic texture undergoing pancreaticoduodenectomy. Patients will be randomized to receive either standard pancreaticojejunostomy (control group) or pancreaticojejunostomy with modified N-butyl-2-cyanoacrylate application (intervention group).

The intervention group will receive 1-2 mL of modified N-butyl-2-cyanoacrylate applied topically to the pancreatic stump and anastomosis site during pancreaticojejunostomy. The control group will receive standard duct-to-mucosa pancreaticojejunostomy without adhesive. All patients will receive standardized perioperative care, including prophylactic antibiotics and drain management per ISGPF guidelines.

Follow-up will include daily amylase measurements in drains (days 1,3,5), CT imaging if POPF suspected.

Interventions

• Drug Pancreaticojejunostomy with Modified N-Butyl-2-Cyanoacrylate (Glubran® 2)
  * Standard duct-to-mucosa pancreaticojejunostomy performed * Application of 0.5-1.0 mL modified N-butyl-2-cyanoacrylate around the anastomotic site * Adhesive applied circumferentially around the pancreaticojejunal anastomosis * Allow 2-3 minutes for polymerization before proceeding * Standard placement of peritoneal drains
• Procedure Standard(duct-to-mucosa) Pancreaticojejunostomy
  * Patients undergo duct-to-mucosa pancreaticojejunostomy without additional adhesive following pancreaticoduodenectomy. * Standard placement of peritoneal drains * All other aspects of surgical care identical to experimental arm

Primary outcome measures

• Incidence of Postoperative Pancreatic Fistula (POPF). [Time frame: 30 days post-surgery.]

Secondary outcome measures (6)

• Time to POPF resolution. [Time frame: 90 days post-surgery.]
• Postoperative complications [Time frame: 30 days post-surgery]
• Reoperation Rate [Time frame: 90 days post-surgery.]
• Length of Hospital Stay [Time frame: Up to 90 days]
• Incidence of postpancreatectomy Hemorrhage [Time frame: 30 days post-surgery]
• Mortality Rate [Time frame: 90 days post-surgery]

Eligibility criteria

Inclusion criteria

• Patients scheduled for elective pancreaticoduodenectomy for malignant lesions.
• Intraoperative confirmation of soft pancreatic texture (by surgeon palpation; friable, non-fibrotic pancreas).
• Age 18-75 years .
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate organ function defined as:

Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count ≥ 1,500/μL Platelet count ≥ 100,000/μL Total bilirubin ≤ 3 times upper limit of normal Alanine transaminase (ALT) /Alanine transaminase (ALT)( ≤ 5 times upper limit of normal Serum creatinine ≤ 1.5 times upper limit of normal

• Informed consent provided.
• Willingness to comply with study procedures and follow-up requirements.

Exclusion criteria

• Hard pancreatic texture (intraoperative surgeon assessment).
• Emergency surgery.
• Previous pancreatic surgery or pancreatic anastomosis.
• Intraoperative identification of unresectable disease
• Known allergy to cyanoacrylate or components.
• Pregnancy or lactation.
• Active infection or sepsis.
• Inability to comply with follow-up.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Liver and GIT hospital , Minia University — Minya

Publications

• Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, Del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-Del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CM, Wolfgang CL, Yeo CJ, Salvia R, Buchler M; Int PMID 28040257
• Gaspar AF, Kemp R, Sankarankutty AK, Lopes Junior JR, Filho JAF, Avezum VAPAF, de Assis Mota G, Nunes AA, Dos Santos JS. Influence on Postoperative Results and Cost-effectiveness of Using Cyanoacrylate Glue for Pancreaticojejunal Anastomosis After Duodenopancreatectomy. Pancreas. 2025 Aug 1;54(7):e610-e617. doi: 10.1097/MPA.0000000000002479. PMID 40127250

Identifiers

NCT: NCT07155525 · 1319/10/2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗