Reduced Pancreatic Fistula Rate Following Pancreaticoduodenectomy: Trial on Pancreaticogastrostomy Versus Pancreaticojejunostomy

Tumors Clinical Trial

Official title:

Reduced Postoperative Pancreatic Fistula Rate Following Pancreaticoduodenectomy; Multicentric Randomized Controlled Trial on Pancreaticogastrostomy vs. Pancreaticojejunostomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00830778
• Other study ID #: S51480
• Status: Completed
• Phase: Phase 3
• First received: January 27, 2009
• Last updated: September 11, 2012
• Start date: June 2009
• Est. completion date: September 2012

Study information

• Verified date: September 2012
• Source: University Hospital, Gasthuisberg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

The incidence of complications after pancreaticoduodenectomy (PD) is around 50 %. The postoperative course after PD is strongly dependent of the occurrence of pancreatic fistula (POPF), which determines postoperative mortality, length of hospital stay and costs. The incidence of POPF after PD is dependent of its definition, and is reported in up to 20% of patients.

There is disagreement on whether to perform a pancreaticojejunostomy (PJ) or a pancreaticogastrostomy (PG) after PD. The aim of the current randomized controlled trial is to study whether PG significantly reduces the rate of POPF following PD for pancreatic or peri-ampullary tumours. Secondary endpoints are the reduction of overall postoperative complication rate and their severity.

Description:

Therapeutic intervention

• Surgeons who have performed a minimum of five (5) PG and PJ procedures can include patients in this randomized trial.

• Any dissection device or technique is allowed.

• Pancreatic anastomosis (PG or PJ)

• 1-layer or 2-layer anastomosis is allowed but has to be registered

• mono-filament and/or poly-filament suture material is allowed but has to be registered

• no pancreatic stent will be placed

• Drainage: one (1) or more closed drain(s) with or without suction is allowed in the vicinity of the pancreatic anastomosis

• Enteral tube feeding (tube positioned in the jejunum at the time of surgery, and distal to the pancreatic anastomosis) as well as total parenteral nutrition (TPN) is allowed

• Gastrostomy tube (percutaneous) is allowed

• Somatostatin: start intra-operatively and administered for seven (7) days after surgery at a dose of 6 mg/d

• Prophylactic use of antibiotics during 24h post-operatively

• Prophylactic use of Ranitidine as well as any PPI (proton pump inhibitor) is allowed to prevent peptic ulcer

Clinical evaluation and assessment criteria

• The number and type of POPF will be recorded according to the ISGPF guidelines and based on findings on day 3 (three) after surgery

• The number and type of postoperative complications will be recorded. The therapy-oriented severity grading system (TOSGS) of complications will be used and complications will be allocated to surgical (SSC) and non-surgical site (NSSC) complications

• The adequacy of the surgical resection margins (pR0) and the magnitude of the tumour-free resection margin (millimetres) will be monitored

• Postoperative length of hospital stay (LOS) will be registered

Patient randomization and registration procedure (randomization lists attached)

• This is a multicentric randomized controlled trial.

• Patient randomization will be done intra-operatively since a substantial number of patients could be dropped out intra-operatively because of the presence of unexpected intra-abdominal metastases at the time of surgery.

• Patient stratification will be performed for each centre and will be based on the diameter of the pancreatic duct. A pancreatic duct at the level of the surgical transsection margin measuring 3 millimetres or less in diameter is defined as being a "soft pancreas". A pancreatic duct measuring more than 3 millimetres is defined as a "hard pancreas".

• A prospective registration of following parameters will be performed: intra-operative diameter of the pancreatic duct at the surgical transection margin, diameter of the pancreas at the surgical transection margin, pancreatic tissue consistency assessed by the surgeon: soft vs. hard, post-operative pathology parameters.

Statistical analysis and sample size calculation based on a stratified design

• 40% of patients are expected to have a hard pancreas and 60% a soft pancreas.

• It is assumed that the magnitude of the effect of the intervention (PJ vs. PG) on the POPF rate, expressed as an odds ratio (OR), is similar in both strata.

• The needed sample size is calculated to have 80% power to detect a common odds ratio of 2.7. POPF rates of 12% and 20% are assumed after PJ within the hard and soft pancreas stratum respectively (yielding 4.8% and 8.4% after PG). Note that, given the unequal size strata, this leads to an expected POPF rate of 16.8% after PJ and 7% after PG (≈12% POPF overall).

• A 2-sided (with alpha=5%) Mantel-Haenszel test of OR=1 for stratified 2x2 tables is planned

• 168 patients are required per group (total patient population 336)

• Expected duration of recruitment: 3-4 years

• An interim analysis will be performed annually (i.e. after inclusion of 1/3 and 2/3 of the patients) to to allow early stop of the study (or accrual of patients in a specific treatment group) due to rejection of the null hypothesis. Using the O'Brien-Fleming method (O'Brien and Fleming 1979) results in respectively |3.471|, |2.454| and |2.004| as critical values for the Z-statistic at the three analysis moments. Otherwise stated, p-values are declared significant if <.00052, <0.0141 and <0.0451 at respectively the first interim analysis, the second interim analysis and at the final analysis.

• Exact 95% confidence intervals will be calculated for the POPF and post-operative complication rates within each stratum. A stratified Mann-Whitney U test will be used for the TOSGS grading.

Translational research: optional Prognostic relevance of gene expression profiling in pancreatic cancer: analyses will be performed at UZ.Leuven/KU.Leuven (project coordinator B.Topal)

• Fresh tissue samples from pancreatic cancer and from non-tumoral pancreatic tissue will be stored in RNA-later (samples in 2 separate tubes; 5-10 volumes of RNA-later)

• Sample tubes will be transported (or picked up by the coördinator's research team), within 3 days from sampling, to be stored in -80°C for further analyses

Recruitment information / eligibility

• Status: Completed
• Enrollment: 336
• Est. completion date: September 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients, male or female, who undergo PD for a pancreatic or peri-ampullary tumor

• Age between 18 to 85 years

• Patients with and without pre-operative biliary drainage (for obstructive jaundice)

• Concomitant surgical procedures such as simultaneous colonic resection etc.

• Reconstruction of the portal vein or superior mesenteric vein

Exclusion Criteria:

• Age < 18years

• Pregnancy

• Pre-operative radiotherapy

• PD for IPMT

• PD for chronic pancreatitis

• PD for pancreatic trauma

• PD for post-ERCP complications

• Any arterial reconstruction at the time of surgery

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Fistula
• Tumors

Intervention

Procedure:
• Pancreaticojejunostomy
Pancreaticojejunostomy (PJ) reconstruction/anastomosis
• Pancreaticogastrostomy
Pancreaticogastrostomy (PG) reconstruction/anastomosis

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg	Leuven

Sponsors (11)

Lead Sponsor	Collaborator
Baki Topal	Clinique Saint Joseph, Liège, Erasme ULB, Brussels, General Hospital Groeninge, Jan Palfijn, Antwerp, Jolimont, Brussels, Monica, Deurne, St.Jan, Brugge, St.Lucas, Brugge, Université Catholique de Louvain, University Hospital, Antwerp

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction of clinical postoperative pancreatic fistula (POPF) rate		3 years	No
Secondary	Reduction of overall postoperative pancreatic fistula rate		3 years	No
Secondary	Reduction of the severity of postoperative complications		3 years	No