Clinical trial NCT03631173: Monitoring of patIents With Microdialysis Following Pancreaticoduodenectomy
Official title: Monitoring of patIents With Microdialysis Following Pancreaticoduodenectomy - a Randomized Controlled Trial. THE MINIMUM STUDY
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Pancreatic Cancer
Pancreatic Neoplasms
Biliary Tract Cancer
Duodenal Cancer
Pancreatic Fistula
Keywords: Pancreaticoduodenectomy
Pancreatectomy
Anastomosis, Surgical
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2018-08-15
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2-armed, multicenter, randomized, open label, parallel-group controlled trial (RCT)
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Total hospital stay
timeFrame: 30 days after surgery - postoperative day 30
Secondary outcomes:
measure: Length of stay at the primary hospital
timeFrame: 30 days after surgery - postoperative day 30
measure: Concentration of Lactate (mM), Pyruvate (microM), Glycerol (microM), Glucose (mM) in microdialysate
timeFrame: 30 days after surgery - postoperative day 30
measure: Concentration of inflammatory markers in microdialysate
timeFrame: 30 days after surgery - postoperative day 30
measure: Concentration of inflammatory markers in serum
timeFrame: 30 days after surgery - postoperative day 30
measure: Patient-reported quality of life questionnaire - total score assessed by the Abdominal surgery Impact scale by summing subscores
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported quality of life questionnaire - subgroup score Physical limitations assessed by the Abdominal surgery Impact scale
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported quality of life questionnaire - subgroup score Functional impairment assessed by the Abdominal surgery Impact scale
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported quality of life questionnaire - subgroup score Pain assessed by the Abdominal surgery Impact scale
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported quality of life questionnaire - subgroup score Visceral Function assessed by the Abdominal surgery Impact scale
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported quality of life questionnaire - subgroup score Sleep assessed by the Abdominal surgery Impact scale
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported quality of life questionnaire - subgroup score Psychological function assessed by the Abdominal surgery Impact scale
timeFrame: From inclusion to 90-days after surgery
measure: Patient-reported pain questionnaire - total score assessed by the McGill Pain Questionnaire-2 (SF-MPQ-2)
timeFrame: From inclusion to 90-days after surgery
measure: Expenses (Euros) per patient used during total hospital stay
timeFrame: 30 days after surgery - postoperative day 30
measure: Daily assessement of microdialysis catheter malfunction during admission at hospital, at an average of 10 days after surgery
timeFrame: From surgery end to discharge from primary hospital, at an average of 10 days after surgery
measure: Risk factors of postoperative pancreatic fistula at discharge from hospital, at an average 10 days after surgery
timeFrame: From surgery end to discharge from primary hospital at hospital, at an average of 10 days after surgery
measure: Risk factors of postoperative pancreatic fistula at 30 days after surgery
timeFrame: From surgery end to 30 days after surgery
measure: Risk factors of postoperative pancreatic fistula at 90 days after surgery
timeFrame: From surgery end to 90 days after surgery
Other outcomes:
measure: Time before postoperative fistula is diagnosed (hours)
timeFrame: End of surgery to 30 days postoperative
measure: Total quantity (μg/mg) of vasoactive medications at discharge at an average of 10 days after surgery
timeFrame: From surgery end to discharge from primary hospital at an average of 10 days after surgery
measure: Number of patients with Pancreatic Fistula
timeFrame: 30 days after surgery - postoperative day 30
measure: Number of patients with Biliary Fistula
timeFrame: 30 days after surgery - postoperative day 30
measure: Number of patients with gastroenteric Fistula
timeFrame: 30 days after surgery - postoperative day 30
measure: 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
timeFrame: From surgery end to discharge from primary hospital at an average of 10 days after surgery
measure: Postoperative complications
timeFrame: From inclusion to 90-days after surgery
measure: Fluid Balance (ml) during hospital admission at an average of 10 days after surgery
timeFrame: From anesthesia start to discharge from primary hospital at an average of 10 days after surgery
measure: Number of patients discharged to home/self care at an average of 10 days after surgery
timeFrame: At discharge at an average of 10 days after surgery
measure: Number of patients discharged to home but with home health service at an average of 10 days
timeFrame: At discharge at an average of 10 days after surgery
measure: Number of patients discharged/transferred to nursing home at an average of 10 days
timeFrame: At discharge at an average of 10 days after surgery
measure: Number of patients discharged/transferred to an inpatient rehabilitation facility at an average of 10 days
timeFrame: At discharge at an average of 10 days after surgery
measure: Number of patients expired at an average of 10 days
timeFrame: At discharge at an average of 10 days after surgery
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Espen Lindholm, ph.d
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.