Intrapapillary Botulinum Toxin Injection for PREvention of Post-surgical PAncREactic Fistula

NCT04220931 | Recruiting DMC

• 1 other identifier: P170913J
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. In its current definition (drain output of any measurable fluid \>= postoperative day 3 with amylase content \>3 times the serum amylase activity and with clinical consequence), the incidence of postoperative PF is between 15 and 30 %. Most POPF resolve spontaneously but when refractory POPF occurs, it may lead to severe complications. POPF severity is graded as follows: grade B in case of change in medical management: infection without organ failure, specific medication (total parenteral nutrition, somatostatin analogs, antibiotics), persistent drainage \> 3 weeks, angiographic procedure for bleeding, prolonged hospital stay; grade C in case of reoperation or PF-related organ failure or death. No specific prophylactic treatment of POPF is currently recommended by clinical guidelines. In clinical research, many prophylactic strategies have been attempted with partial efficacy. Endoscopic pancreatic sphincterotomy with plastic stent placement is effective in pre-and postoperative management of pancreatic fistula but with the need of a highly competent interventional endoscopist. Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic sphincterotomy without any morbidity. A recent phase I/II prospective study has shown promising results in this indication, with no clinically relevant pancreatic fistula when botulinum toxin was injected. Based on this observation we hypothesize that intrapapillary botulinum toxin injection during an endoscopic procedure before surgery could be effective for the prevention of post-surgical pancreatic fistula

Conditions

Distal Pancreatectomy; Postoperative Pancreatic Fistula

Keywords

distal pancreatectomy

Outcome Measures

Primary Outcomes (1)

• number of postoperative pancreatic fistula

  Clinically relevant POPF (grade B and C) in the 3 months after Distal Pancreatectomy

  3 months

Secondary Outcomes (12)

• number of postoperative pancreatic fistulas grade B

  3 months

• number of postoperative pancreatic fistulas grade C

  3 months

• Quantity of Biochemical leak after surgery

  3 months

• number of Postoperative complications

  3 months

• CLAVIEN-DINDO classification for post-surgical morbidity

  3 months

Study Arms (2)

botulinum toxin injection

EXPERIMENTAL

Injection of Botulinum toxin A 100 UI, single dose administration, in the major papilla, in the Oddi sphincter, during upper gastrointestinal endoscopy. The endoscopic procedure will be performed under unconscious sedation with intravenous injection of propofol by an anesthesiologist.

Drug: botulinum toxin injection

standard care

NO INTERVENTION

standard care (no endoscopy)

Interventions

botulinum toxin injection DRUG

injection of Botulinum toxin A 100 UI, single dose administration, in the major papilla, in the Oddi sphincter, during upper gastrointestinal endoscopy.

botulinum toxin injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with scheduled distal pancreatectomy for any indication: open or laparoscopic distal pancreatectomy with or without splenectomy
• Age ≥ 18years

You may not qualify if:

• History of myasthenia gravis or Eaton-Lambert syndrome
• Inflammatory myositis \<2 years or preexisting motor neuron disease or neuropathies
• ASA score \> III
• Pregnancy or lactation
• Altered anatomy of the duodenum and/or the major papilla (prior surgery, prior endoscopic sphincterotomy)
• Scheduled pancreaticoduodenectomy (Whipple procedure)
• Scheduled total pancreatectomy
• Scheduled central pancreatectomy
• Scheduled pancreatic enucleation
• Calcified chronic pancreatitis (suspected on preoperative cross-sectional imaging)
• Pancreas divisum (suspected on preoperative cross-sectional imaging)
• Toxin botulinum contraindications (hypersensitivity to albumin or to saccharose, infection or inflammation at the injection site concerned, generalized muscle weakness)
• Preoperative administration of somatostatin analogs: for long-acting somatostatin analogs, a 1-month washout period is necessary; for short-acting somatostatin analogs, a 24-hours washout period is necessary
• Any kind of surgical method to reinforce the pancreatic stump:
• Use of a bioabsorbable patch

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

PRAT

Clichy, 92110, France

RECRUITING

MeSH Terms

Interventions

Botulinum Toxins

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Frederic Prat, prof

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frederic Prat, Prof

CONTACT

0033(1)40875663; frederic.prat@aphp.fr

Alain Sauvanet, Prof

CONTACT

alain.sauvanet@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 7, 2020
• Study Start: March 27, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: July 10, 2023

Record last verified: 2023-07

Locations

FR (1)