Ignite Creation Date:
2025-12-18 @ 9:34 AM
Ignite Modification Date:
2025-12-23 @ 8:51 PM
Study NCT ID:
NCT00830778
Status:
None
Last Update Posted:
2012-09-12 00:00:00
First Post:
2009-01-27 00:00:00
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Reduced Pancreatic Fistula Rate Following Pancreaticoduodenectomy: Trial on Pancreaticogastrostomy Versus Pancreaticojejunostomy
Sponsor:
None
Organization:
Study Overview
Official Title:
Reduced Postoperative Pancreatic Fistula Rate Following Pancreaticoduodenectomy; Multicentric Randomized Controlled Trial on Pancreaticogastrostomy vs. Pancreaticojejunostomy
Status:
None
Status Verified Date:
2012-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
* 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: