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

This study has been completed.
Sponsor:
Collaborators:
Erasme ULB, Brussels
Jolimont, Brussels
St.Lucas, Brugge
General Hospital Groeninge
Universite Catholique Louvain (UCL), Brussels
St.Joseph, Liège
University Hospital, Antwerp
Jan Palfijn, Antwerp
St.Jan, Brugge
Monica, Deurne
Information provided by (Responsible Party):
Baki Topal, University Hospital, Gasthuisberg
ClinicalTrials.gov Identifier:
NCT00830778
First received: January 27, 2009
Last updated: September 11, 2012
Last verified: September 2012

January 27, 2009
September 11, 2012
June 2009
August 2012   (final data collection date for primary outcome measure)
Reduction of clinical postoperative pancreatic fistula (POPF) rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Reduction of postoperative pancreatic fistula (POPF) rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00830778 on ClinicalTrials.gov Archive Site
  • Reduction of overall postoperative pancreatic fistula rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Reduction of the severity of postoperative complications [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Reduction of overall postoperative complication rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Reduction of the severity of postoperative complications [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Reduced Pancreatic Fistula Rate Following Pancreaticoduodenectomy: Trial on Pancreaticogastrostomy Versus Pancreaticojejunostomy
Reduced Postoperative Pancreatic Fistula Rate Following Pancreaticoduodenectomy; Multicentric Randomized Controlled Trial on Pancreaticogastrostomy vs. Pancreaticojejunostomy

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.

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
Interventional
Phase 3
Allocation: Randomized
Primary Purpose: Treatment
Tumors
  • Procedure: Pancreaticojejunostomy
    Pancreaticojejunostomy (PJ) reconstruction/anastomosis
  • Procedure: Pancreaticogastrostomy
    Pancreaticogastrostomy (PG) reconstruction/anastomosis
  • Experimental: PG anastomosis
    Pancreaticogastrostomy (PG) reconstruction/anastomosis after pancreaticoduodenectomy (PD)
    Intervention: Procedure: Pancreaticogastrostomy
  • Active Comparator: PJ anastomosis
    Pancreaticojejunostomy (PJ) reconstruction/anastomosis after pancreaticoduodenectomy (PD)
    Intervention: Procedure: Pancreaticojejunostomy
Bertrand C, Squifflet JP, Gys T, Berrevoet F, Jehaes C, Lerut T, Malaise J, Topal B. The Society for Internet-based Scientific Studies: a new platform to promote multicentric studies in the Royal Belgian Society for Surgery. Acta Chir Belg. 2010 Jan-Feb;110(1):3-5. Erratum in: Acta Chir Belg. 2010 Mar-Apr;110(2):261.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
336
September 2012
August 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Belgium
 
NCT00830778
S51480
Yes
Baki Topal, University Hospital, Gasthuisberg
Baki Topal
  • Erasme ULB, Brussels
  • Jolimont, Brussels
  • St.Lucas, Brugge
  • General Hospital Groeninge
  • Universite Catholique Louvain (UCL), Brussels
  • St.Joseph, Liège
  • University Hospital, Antwerp
  • Jan Palfijn, Antwerp
  • St.Jan, Brugge
  • Monica, Deurne
Study Director: Baki Topal, MD, PhD Universitaire Ziekenhuizen Leuven
Principal Investigator: Claude Bertrand, MD Hospital Jolimont, Brussels
Principal Investigator: Jean Closset, MD, PhD Hospital Erasme (ULB), Brussels
Principal Investigator: Henk Thieren, MD AZ. St.Lucas, Brugge
Principal Investigator: Franky Vansteenkiste, MD General Hospital Groeninge
Principal Investigator: Jean-Francois Gigot, MD, PhD Universite Catholique Louvain (UCL), Brussels
Principal Investigator: Joseph Weerts, MD St.Joseph Hospital, Liège
Principal Investigator: Geert Roeyen, MD University Hospital Antwerp, Antwerp
Principal Investigator: Marc Janssens, MD J.Palfijn Hospital, Antwerp
Principal Investigator: Tom Feryn, MD St.Jan Hospital, Brugge
Principal Investigator: Steven Pauli, MD Monica Hospital, Deurne
University Hospital, Gasthuisberg
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP