PERT to Improve Quality of Life in Patients Undergoing Pancreaticoduodenectomy: A Pilot Randomized Controlled Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pancreatic Insufficiency

Intervention / Treatment
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* Drug: PERT at discharge
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged >18 years Willing and able to provide informed consent and/or have a substitute decision maker (SDM) provide informed consent on behalf of the participant Planned PD for any indication AND, at randomization PD performed Discharge planned within 21 days of surgery Exclusion Criteria: Contraindication to PERT including: Hypersensitivity to porcine protein, pancreatic enzymes or any excipients History of fibrosing colonopathy Unable to tolerate oral medication Current use of PERT OR, at randomization Use of PERT at the time of randomization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PERT plus Standard of Care<br>Initiation of PERT at time of discharge post pancreaticoduodenectomy with dose escalation upon symptom presentation | Drug: PERT at discharge<br>* 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.<br>* Other names: PrCREON MINIMICROSPHERES®25 or similar (PrCotazym® ECS, PrPANCREASE® MT, PrVIOKACE™);Other: Standard of Care<br>* 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.<br>|
| Other: Standard of Care<br>Standard of care (no PERT) until presentation of PEI symptoms. | Other: Standard of Care<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreaticoduodenectomy, Pancreatic enzyme replacement therapy