Monitoring of patIents With Microdialysis Following Pancreaticoduodenectomy (MINIMUM)

Monitoring of patIents With Microdialysis Following Pancreaticoduodenectomy - a Randomized Controlled Trial. THE MINIMUM STUDY

A pancreaticoduodenectomy is performed in patient with pancreatic cancer. The most common and serious complication is leakage between the intestine and the remnant pancreas after this procedure. It occurs in 20-30%. The result is often prolonged hospital and ICU stay, reoperations and deaths (3-5%). To detect a leakage early before the patient becomes seriously ill, thereby initiating treatment is therefore very important. By inserting a thin microdialysis catheter near the anastomosis between pancreas and intestine before closure of the abdominal wall, the investigators will analyze substances such as lactic acid, pyruvate, glycerol, etc. and if these substances may reveal anastomosis leakage at an early stage. Observational studies have shown that if a leakage occurs, glycerol concentration in the microdialysate will rise significant after few hours, and changes in lactic acid and pyruvate values will change as a sign of inflammation. The investigators want to conduct a randomized study comparing patients undergoing pancreaticoduodenectomy and using microdialysis in half of the included population.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Neoplasms; Pancreatic Cancer; Pancreatic Fistula; Biliary Tract Cancer; Duodenal Cancer
• Intervention / Treatment: Procedure: Surgical og radiological intervention, antibiotics

Detailed Description

Anastomotic leakage after pancreaticoduodenectomy is a feared complication with substantial mortality and morbidity. Treatment of a postoperative pancreatic fistula can be difficult and management may range from a simple observation with or without percutaneous drainage, to the urgent need for reoperation and management of abdominal sepsis with organ failure and prolonged intensive care. To diagnose a pancreatic fistula may have a delay of several days. The risk of death and severe morbidity raises considerable from a biochemical pancreatic fistula compared to the most serious form, a grade C. Also, the cost of managing a patient with a fistula is 1.3-6 times more than a patient with no complications after PD.

Microdialysis is a promising tool in patients who undergoes pancreaticoduodenectomy for early detection of postoperative pancreatic fistula development. The technique may reveal an fistula before severe symptoms occur and before the complication gives the patient serious and life-threatening symptoms. Earlier intervention of the postoperative pancreatic fistula may lead to better prognosis, less reoperations and interventions and shorter stay at the ICU/hospital. By monitoring intraperitoneal metabolites (glycerol, lactate, pyruvate and glucose) close to the pancreaticojejunostomy, signs of a leakage may be discovered in few hours, thereby make it possible for early intervention and prevent developement of serious progression of morbidity. The investigators want to perform a randomized study where half of the patients will receive a microdialysis catheter implanted close to the pancreaticoduodenal anastomosis before closure of the abdomen. At certain timepoints postoperatively microdialysate will be analyzed for glycerol, lactate, pyruvate and glucose and the data will be used in the decisionmaking of diagnosing a pancreatic anastomosis leakage in addition to standard management. The other half of the patients will not receive a microdialysis catheter and the decisionmaking will only be based on standard management (ie. inflammation markers in blood samples, amylase in drainage fluid).

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be scheduled for a pancreaticoduodenectomy
• Subject must be ≥ 18 years
• Able to give written signed informed consent
• Investigator's assessment that the patient is able to understand, comply and follow the instructions needed to successfully participate in this trial

Exclusion Criteria:

• Allergic to Voluven® (Fresenius Kabi AS, Halden, Norway) and contrast given during CT scan
• Another study interfering with current study
• Pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patient with microdialysis; Intervention group - Patients will receive an intraperitoneal microdialysis catheter and will be monitored consecutively by microdialysis. The surgeon is familiar with the current microdialysis results at any time during the study period. The surgeon may intervene based on traditional symptoms and signs plus predetermined values of the microdialysis results.	Procedure: Surgical og radiological intervention, antibiotics; Intervention might be a new drainage catheter, replacement of old drainage catheter, reoperation, somatostatin- and antibiotic administration.
No Intervention: Patient without microdialysis; The control group - The patients will not receive a microdialysis catheter. The patients are monitored according to current standards of care and the surgeon may intervene based only on traditional symptoms and signs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total hospital stay	Number of days from end of surgery to hospital discharge (at any hospital)	30 days after surgery - postoperative day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay at the primary hospital	Length of stay at the primary hospital and ICU. Number of days from initial operation to primary hospital discharge.	30 days after surgery - postoperative day 30
Concentration of Lactate (mM), Pyruvate (microM), Glycerol (microM), Glucose (mM) in microdialysate	Concentration of Lactate, Pyruvate, Glycerol, Glucose in microdialysate in relation to patients with or without anastomosis leakage	30 days after surgery - postoperative day 30
Concentration of inflammatory markers in microdialysate	Concentration of inflammatory markers in microdialysate in relation to patients with or without anastomosis leakage	30 days after surgery - postoperative day 30
Concentration of inflammatory markers in serum	Concentration of inflammatory markers in serum in relation to patients with or without anastomosis leakage	30 days after surgery - postoperative day 30
Patient-reported quality of life questionnaire - total score assessed by the Abdominal surgery Impact scale by summing subscores	Total score - Abdominal surgery Impact scale. The summative scores for the scale range from 18 to 126, with higher scores indicating better quality of life	From inclusion to 90-days after surgery
Patient-reported quality of life questionnaire - subgroup score Physical limitations assessed by the Abdominal surgery Impact scale	Subgroup score Physical limitations - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating better physical ability	From inclusion to 90-days after surgery
Patient-reported quality of life questionnaire - subgroup score Functional impairment assessed by the Abdominal surgery Impact scale	Subgroup score Functional impairment - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating better functional ability	From inclusion to 90-days after surgery
Patient-reported quality of life questionnaire - subgroup score Pain assessed by the Abdominal surgery Impact scale	Subgroup score Pain - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more pain	From inclusion to 90-days after surgery
Patient-reported quality of life questionnaire - subgroup score Visceral Function assessed by the Abdominal surgery Impact scale	Subgroup score Visceral Function - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more Visceral dysfunction	From inclusion to 90-days after surgery
Patient-reported quality of life questionnaire - subgroup score Sleep assessed by the Abdominal surgery Impact scale	Subgroup score Sleep - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more sleep dysfunction	From inclusion to 90-days after surgery
Patient-reported quality of life questionnaire - subgroup score Psychological function assessed by the Abdominal surgery Impact scale	Subgroup score Psychological function - Abdominal surgery Impact scale. The summative scores for the scale range from 3 to 18, with higher scores indicating more psychological dysfunction	From inclusion to 90-days after surgery
Patient-reported pain questionnaire - total score assessed by the McGill Pain Questionnaire-2 (SF-MPQ-2)	Total score - McGill Pain Questionnaire-2 (SF-MPQ-2). Subgroup score Psychological function - Abdominal surgery Impact scale. The summative scores ranging from 0 to 45, with higher score indicating more pain	From inclusion to 90-days after surgery
Expenses (Euros) per patient used during total hospital stay	Number of Euros used in patient undergoing pancreaticoduodenectomy With or without microdialysis catheter	30 days after surgery - postoperative day 30
Daily assessement of microdialysis catheter malfunction during admission at hospital, at an average of 10 days after surgery	Number of catheter which are not functioning	From surgery end to discharge from primary hospital, at an average of 10 days after surgery
Risk factors of postoperative pancreatic fistula at discharge from hospital, at an average 10 days after surgery	Numbers of risk factors of postoperative pancreatic fistula in relation to patients with or without anastomosis leakage	From surgery end to discharge from primary hospital at hospital, at an average of 10 days after surgery
Risk factors of postoperative pancreatic fistula at 30 days after surgery	Numbers of risk factors of postoperative pancreatic fistula in relation to patients with or without anastomosis leakage	From surgery end to 30 days after surgery
Risk factors of postoperative pancreatic fistula at 90 days after surgery	Numbers of risk factors of postoperative pancreatic fistula in relation to patients with or without anastomosis leakage	From surgery end to 90 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time before postoperative fistula is diagnosed (hours)	Hours from end of surgery to diagnosis of postoperative pancreatic fistula	End of surgery to 30 days postoperative
Total quantity (μg/mg) of vasoactive medications at discharge at an average of 10 days after surgery	Amount of vasoactive medication during surgery and postoperatively until discharge from the hospital where the surgery was performed.	From surgery end to discharge from primary hospital at an average of 10 days after surgery
Number of patients with Pancreatic Fistula	Number of patients with Pancreatic Fistula	30 days after surgery - postoperative day 30
Number of patients with Biliary Fistula	Number of patients with Biliary Fistula	30 days after surgery - postoperative day 30
Number of patients with gastroenteric Fistula	Number of patients with gastroenteric Fistula	30 days after surgery - postoperative day 30
Daily measurements during hospital admission of pancreatic amylase (U/L) and bilirubin (µmol/L ) concentrations in drainage fluid and in serum, at an average og 10 days after surgery	Pancreatic amylase and bilirubin concentrations in drainage fluid and in serum	From surgery end to discharge from primary hospital at an average of 10 days after surgery
Postoperative complications	Number of patients with postoperative complications during total hospital stay	From inclusion to 90-days after surgery
Fluid Balance (ml) during hospital admission at an average of 10 days after surgery	Diuresis and amount of fluid given i.v. during surgery and postoperatively until discharge from the primary hospital	From anesthesia start to discharge from primary hospital at an average of 10 days after surgery
Number of patients discharged to home/self care at an average of 10 days after surgery	Patient's discharge disposition - number of patients Discharged to home/self care	At discharge at an average of 10 days after surgery
Number of patients discharged to home but with home health service at an average of 10 days	Patient's discharge disposition - number of patients Discharged to home but with home health service	At discharge at an average of 10 days after surgery
Number of patients discharged/transferred to nursing home at an average of 10 days	Patient's discharge disposition - number of patients Discharged/transferred to nursing home	At discharge at an average of 10 days after surgery
Number of patients discharged/transferred to an inpatient rehabilitation facility at an average of 10 days	Discharged to an inpatient rehabilitation facility	At discharge at an average of 10 days after surgery
Number of patients expired at an average of 10 days	Patient's discharge disposition - expired	At discharge at an average of 10 days after surgery

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Espen Lindholm, ph.d, Oslo University Hospital

Publications and helpful links

General Publications

• Lindholm E, Ekiz N, Tonnessen TI. Monitoring of patients with microdialysis following pancreaticoduodenectomy-the MINIMUM study: study protocol for a randomized controlled trial. Trials. 2021 May 7;22(1):329. doi: 10.1186/s13063-021-05221-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2019
• Primary Completion (Actual): August 1, 2021
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pancreatectomy; Pancreaticoduodenectomy; Anastomosis, Surgical
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Pathological Conditions, Anatomical; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Duodenal Diseases; Digestive System Fistula; Fistula; Pathological Conditions, Signs and Symptoms; Biliary Tract Neoplasms; Pancreatic Neoplasms; Duodenal Neoplasms; Pancreatic Fistula; Anti-Infective Agents; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Anti-Bacterial Agents
• Other Study ID Numbers: 2018/1334

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan for individual participant data (IPD).

Drug and device information, study documents

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