PERT to Improve Quality of Life in Patients Undergoing Pancreaticoduodenectomy: A Pilot Randomized Controlled Trial (PERQ-UP)

Pancreatic Enzyme Replacement Therapy to Improve Quality of Life in Patients Undergoing Pancreaticoduodenectomy: A Pilot Randomized Controlled Trial

After pancreas surgery, patients may develop pancreatic exocrine insufficiency (PEI). PEI can be treated with oral pancreatic enzyme replacement therapy (PERT). However, the diagnosis of PEI is difficult and the guidelines about when to start PERT after pancreas surgery are conflicting. This pilot study aims to determine the feasibility of implementing a large-scale clinical trial to definitively evaluate if starting PERT immediately after surgery can improve outcomes in patients undergoing pancreas surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Insufficiency
• Intervention / Treatment: Drug: PERT at discharge; Other: Standard of Care

Detailed Description

After pancreas surgery, patients may develop pancreatic exocrine insufficiency (PEI). This occurs when there are not enough exocrine cells in the pancreas to release enzymes that help with food digestion. Potential symptoms may include bloating, cramping, large and foul-smelling bowel movements (steatorrhea), and other gastrointestinal symptoms like diarrhea, weight-loss, and malnutrition. PEI can be treated with oral pancreatic enzyme replacement therapy (PERT), for example CREON. Many studies have shown that treatment of PEI with PERT is safe, effective, and may improve quality of life, reduce weight loss, improve abdominal symptoms, and may improve overall survival. However, the diagnosis of PEI is difficult and the guidelines about when to start PERT after pancreas surgery are conflicting. This pilot study aims to determine the feasibility of implementing a large-scale clinical trial to definitively evaluate if starting PERT immediately after surgery can improve outcomes in patients undergoing pancreas surgery.

Participants will be recruited from Ontario hospitals using a two-step eligibility process (pre- and post-operatively) and randomized 1:1 to receive either standard of care or PERT plus standard of care. Outcome measures will be collected 1 and 3 months postoperatively.

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences Centre
    • Kingston, Ontario, Canada
      • Kingston General Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • University Health Network

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults aged >18 years
2. Willing and able to provide informed consent and/or have a substitute decision maker (SDM) provide informed consent on behalf of the participant
3. Planned PD for any indication AND, at randomization
4. PD performed
5. Discharge planned within 21 days of surgery

Exclusion Criteria:

1. Contraindication to PERT including:

   1. Hypersensitivity to porcine protein, pancreatic enzymes or any excipients
   2. History of fibrosing colonopathy
   3. Unable to tolerate oral medication
2. Current use of PERT OR, at randomization
3. Use of PERT at the time of randomization

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PERT plus Standard of Care; Initiation of PERT at time of discharge post pancreaticoduodenectomy with dose escalation upon symptom presentation	Drug: PERT at discharge; Starting dose 50,000 units lipase per meal with 3 meals planned per day and 25,000 units of lipase per snack with 2 snacks planned per day. Dose escalation 100,000 units lipase with meals and 50,000 units with snacks.; Other Names: PrCREON MINIMICROSPHERES®25 or similar (PrCotazym® ECS, PrPANCREASE® MT, PrVIOKACE™); Other: Standard of Care; Initiation of PERT if clinical symptoms of PEI develop or worsen. Starting dose 50,000 units lipase per meal with 3 meals planned per day and 25,000 units of lipase per snack with 2 snacks planned per day.
Other: Standard of Care; Standard of care (no PERT) until presentation of PEI symptoms.	Other: Standard of Care; Initiation of PERT if clinical symptoms of PEI develop or worsen. Starting dose 50,000 units lipase per meal with 3 meals planned per day and 25,000 units of lipase per snack with 2 snacks planned per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients screened who consent	Each centre will keep a screening log of all patients who are scheduled to undergo an elective pancreaticoduodenectomy and perform pre-screening to determine eligibility. The number of eligible patients who are approached for and consent to participate, as well as the number of approached eligible patients who decline to participate (and reasons for declining) will be recorded and the proportions will be calculated	Baseline
Proportion of patients screened who meet eligibility criteria	Each centre will keep a screening log of all patients who are scheduled to undergo an elective pancreaticoduodenectomy and perform pre-screening to determine eligibility. The eligibility criteria that are unmet will be recorded, including the additional criteria for randomization. This will be used to calculate proportions.	Baseline
Adherence to PERT	Recorded on participant's medication tracker and calculated as a percentage of expected vs. actual doses taken.	3 months
Adherence to PERT dosing guidelines	Review of medical record for appropriate use of PERT dosing guidelines, comparing actual prescription to dosing guideline	Day 0 (Discharge)
Adherence to PERT dosing guidelines	Review of medical record for appropriate use of PERT dosing guidelines, comparing actual prescription to dosing guideline	1 month
Adherence to PERT dosing guidelines	Review of medical record for appropriate use of PERT dosing guidelines, comparing actual prescription to dosing guideline	3 months
Completeness of dataset	Assessment of completeness of data, loss to follow-up and missing data and reasons for not being able to collect data	3 months
Resource requirement for definitive trial	Each site will complete a survey at the end of the trial to report the amount of time spent on study activities	Study completion (1.5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss	Difference in weight (kg) from baseline	1 month, 3 months
Change in Digestive Symptoms Scale from Baseline	Measured using PAN26 quality of life questionnaire which specific to pancreatic cancer and must be administered in conjunction with QLQ-C30. Scores range from 0 to 100 and consist of functional scales and symptoms scales. A high score on the symptoms scales indicates a high level of symptomatology. A high score on the functional scales indicates a high level of functioning.	1 month, 3 months
Change in Quality of Life from Baseline	Measured using the QLQ-C30 quality of life questionnaires. QLQ-C30 is a validated questionnaire that assesses health-related quality of life (QoL) in cancer patients. Scores for both questionnaires range from 0 to 100 and consist of functional scales and symptoms scales. A high score on the symptoms scales indicates a high level of symptomatology. A high score on the functional scales indicates a high level of functioning.	1 month, 3 months

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Paul Karanicolas, MD, PhD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2023
• Primary Completion (Actual): May 31, 2024
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Pancreaticoduodenectomy; Pancreatic enzyme replacement therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: 3962 (Direktion Lehre und Forschung Insel Spital Bern)

Drug and device information, study documents

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