Early POstoperative BIomarkers in PancreatoDuodenectomy: a Spanish Nationwide Study (EPOBIPD)

Early POstoperative BIomarkers in PancreatoDuodenectomy as Predictors of Complications: a Spanish Nationwide Multicentric Validation Study

AIMS: To recruit a large nationwide Spanish series in order to register PF rate and other common morbidity after PD, and to perform external validation of the aforementioned score, as well as to analyze other postoperative blood parameters and biomarkers associated with complications.

METHODS: Observational prospective and multicentric cohort study to perform external validation of the above-mentioned score. All Spanish centers/units performing PD are invited to include participants. Patients will be consecutively recruited during an 8-10 months period, regardless of their annual volume of pancreatic surgery.

Study variables will be hemogram parameters on POD1 and POD2 (specifically lymphocytes), other parameters and biomarkers (RCP, lactate, procalcitonin, amylase, lipase, albumin) and the common variables concerning PD studies.

LIMITATIONS: Heterogeneity in perioperative management and in blood analysis measuring since this is a multicenter study. Possibility of underestimating the PF rate in patients without surgical drainage. Finally, the cases of mini-invasive approach or pancreatogastrostomy will receive a specific subgroup analysis since the score was designed on a series of open PD and pancreatojejunostomy.

Study Overview

• Status: Recruiting
• Conditions: Pancreaticoduodenectomy
• Intervention / Treatment: Other: No intervention

Detailed Description

BACKGROUND: Complications after pancreatoduodenectomy (PD) are common and pancreatic fistula (PF) is among the most relevant ones. There are few studies analyzing blood parameters determined in the early postoperative period which behave as morbidity predictors. One of them defined a new and simple prognostic score based on lymphocytes count on the first postoperative day (POD1) and reactive C protein (RCP) on POD2. The internal validation statistics of the score designed in the mentioned work were satisfactory. However, that score was described in a short unicentric series

EXPECTED SAMPLE SIZE: Expected sample size is approximately 500 patients, which will show error <7.2% (with 95% confidence) for estimation score´s sensitivity and specificity. We have assumed that the PF rate is around 30%.

QUALITY CONTROL: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for the correct communication and publication of observational studies will be followed. Likewise, in order to validate the aforementioned score, Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) will be added. The only expected failure of the 20 items that compose the TRIPOD is 6b ("notify the actions for masking the analysis"), since it is not applicable in our case.

The inclusion of patients operated on with a mini-invasive approach (laparoscopic or robotic) or the use of other anastomoses (pancreatogastrostomy) or reconstruction (Roux-en-Y) differs from the technique used in the series with which the score was originally defined (allof them, open PD with pancreato-jejunostomy and, mostly part, tutored ducto-mucosal suture and Child's single loop reconstruction). If discrepancies are detected, the corresponding subgroup analysis will be performed. Cases of conversion from a mini-invasive to open approach will be counted as such (intention-to-treat analysis).

• Study Type: Observational
• Enrollment (Anticipated): 525

Contacts and Locations

• Study Contact: Name: Mario Rodriguez-Lopez, MD, PhD; Phone Number: 86266 983420000; Email: mariorodriguezlopez@gmail.com
• Study Contact Backup: Name: Carlos A Jezieniecki-Fernandez, MD; Phone Number: 86266 983420000; Email: carlos.jezieniecki@gmail.com

Study Locations

• Spain
  • Valladolid, Spain, 47003
    • Recruiting
    • Hospital Clínico Universitario
    • Contact: Mario Rodriguez-Lopez, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing PD in Spain

Description

Inclusion Criteria:

• benign or malignant condition requiring surgical treatment by PD.
• Signing the informed consent form

Exclusion Criteria:

• Intra-operative findings of unresectability (pancreatic resection not be completed or palliative procedure performed)
• Other types of pancreatic resection (enucleations, distal and total pancreatectomies), as well as multivisceral resective procedures.
• Intraoperative radiotherapy
• ASA IV patients

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Complete cohort; All patients undergoing PD during study period in all participating center/units in Spain.	Other: No intervention; Blood analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pancreatic fistula rate	Pancreatic fistula including biochemical, grade B and grade C according to ISGPS updated criteria 2016	90 days since PD

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant pancreatic fistula	Pancreatic fistula including grade B and grade C according to ISGPS updated criteria 2016	90 days since PD
Overall complications	Presence of any kind of complications including grades I to V according to Dindo-Clavien Classification	90 days since PD
Severe morbidity	Presence of any kind of complications including grades IIIa to V according to Dindo-Clavien Classification	90 days since PD
Mortality	Patient´s death	90 days since PD
Comprehensive Complication Index	Postoperative morbidity index (0-100 points) obteined by using formula described by Slankamenac et al Ann Surg 2013	90 days since PD

Collaborators and Investigators

• Sponsor: Hospital Clínico Universitario de Valladolid
• Investigators: Principal Investigator: Mario Rodriguez-Lopez, MD, PhD, Hospital Clinico Universitario de Valladolid (España)

Publications and helpful links

General Publications

• Rodriguez-Lopez M, Tejero-Pintor FJ, Bailon-Cuadrado M, Barrera-Rebollo A, Perez-Saborido B, Pacheco-Sanchez D. Impaired immune reaction and increased lactate and C-reactive protein for early prediction of severe morbidity and pancreatic fistula after pancreatoduodenectomy. Hepatobiliary Pancreat Dis Int. 2020 Feb;19(1):58-67. doi: 10.1016/j.hbpd.2019.05.003. Epub 2019 May 20.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2021
• Primary Completion (ANTICIPATED): March 1, 2022
• Study Completion (ANTICIPATED): May 1, 2022

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (ACTUAL): April 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 9, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: SCORE; PANCREATICODUODENECTOMY; COMPLICATIONS; PANCREATIC FISTULA; BIOMARKERS
• Other Study ID Numbers: PI 20-1679

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No