PERT for Pancreatic Insufficiency

(PERQ-UP Trial)

Recruiting at 5 trial locations

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: PERT

Disqualifiers: Hypersensitivity, Fibrosing colonopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 3 months

166 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using pancreatic enzyme replacement therapy (PERT).

What data supports the effectiveness of the treatment PERT for pancreatic insufficiency?

Research shows that PERT (pancreatic enzyme replacement therapy) is effective in improving survival and reducing symptoms related to digestion problems in patients with pancreatic cancer and chronic pancreatitis. In a study, patients with pancreatic cancer who received PERT lived significantly longer than those who did not. ^{1 2 3 4 5}

Is pancreatic enzyme replacement therapy (PERT) generally safe for humans?

Pancreatic enzyme replacement therapy (PERT) has been evaluated for safety in patients with cystic fibrosis and exocrine pancreatic insufficiency. The FDA requires all PERT products to undergo safety studies before approval, and several PERT products have been approved, indicating they are generally considered safe for human use. ^{6 7 8 9 10}

How is the drug PERT different from other treatments for pancreatic insufficiency?

PERT, specifically in the form of pancrelipase delayed-release capsules like CREON, is unique because it provides a controlled release of enzymes to aid digestion, which is crucial for preventing malnutrition and weight loss in patients with exocrine pancreatic insufficiency due to conditions like chronic pancreatitis or pancreatic surgery. ^{2 7 11 12 13}

What is the purpose of this 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.

Research Team

Paul Karanicolas, MD, PhD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for adults over 18 who've had pancreas surgery and are set to leave the hospital within 21 days. They must be able to consent or have someone do it for them. It's not for those already on PERT, with a history of fibrosing colonopathy, current PERT users, those unable to take oral meds, or allergic to porcine protein.

Inclusion Criteria

Planned PD for any indication AND, at randomization

I am older than 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

Exclusion Criteria

I am currently using pancreatic enzyme replacement therapy.

I cannot take medicine by mouth.

I am currently using pancreatic enzyme replacement therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Baseline

Treatment

Participants receive PERT or standard of care post pancreaticoduodenectomy

3 months

Visits at 1 month and 3 months postoperatively

Follow-up

Participants are monitored for safety and effectiveness after treatment

1.5 years

Treatment Details

Interventions

• PERT

Trial Overview The study tests if starting pancreatic enzyme replacement therapy (PERT) right after pancreas surgery helps patients better than the usual care without immediate PERT. The goal is to see if this approach can improve quality of life post-surgery.

Participant Groups

Group I: Standard of Care Experimental Treatment 1 Intervention

Standard of care (no PERT) until presentation of PEI symptoms.

Group II: PERT plus Standard of Care Experimental Treatment 2 Interventions

Initiation of PERT at time of discharge post pancreaticoduodenectomy with dose escalation upon symptom presentation

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

Pancreatic enzyme replacement therapy (PERT) significantly improves fat absorption in patients with chronic pancreatitis, with a coefficient of fat absorption increasing from 63.1 to 83.7, indicating its efficacy in treating exocrine pancreatic insufficiency.

PERT also enhances overall nutritional status and quality of life without significant adverse events, suggesting it is a safe and effective treatment, especially when higher doses or enteric-coated formulations are used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. de la Iglesia-García, D., Huang, W., Szatmary, P., et al.[2022]

Pancreatic enzyme replacement therapy (PERT) significantly improves fat absorption (CFA) in patients with exocrine pancreatic insufficiency (EPI), with a mean difference of 26.56 compared to baseline and 17.97 compared to placebo, based on a meta-analysis of 7 randomized controlled trials involving 282 patients.

The study found that PERT is effective and well-tolerated, with no significant differences in adverse events compared to placebo, suggesting it is a safe treatment option for EPI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis. Gan, C., Chen, YH., Liu, L., et al.[2022]

In a study involving 54 patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis or pancreatic surgery, pancrelipase significantly improved fat absorption (CFA) and nitrogen absorption (CNA) compared to placebo, indicating its efficacy in treating maldigestion.

The safety profile of pancrelipase was comparable to that of placebo, with similar rates of treatment-emergent adverse events, suggesting it is a safe option for patients with EPI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Whitcomb, DC., Lehman, GA., Vasileva, G., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pancreatic enzyme treatment in chronic pancreatitis: Quality of management and adherence to guidelines-A cross-sectional observational study. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pancreatic Enzyme Replacement Therapy in Patients Undergoing First-Line Gemcitabine Plus nab-paclitaxel for Advanced Pancreatic Adenocarcinoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A Multicenter Open-Label Randomized Controlled Trial of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Study design considerations for evaluating the efficacy and safety of pancreatic enzyme replacement therapy in patients with cystic fibrosis. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of a new formulation of pancrelipase delayed-release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double-blind, placebo-controlled, two-period crossover, superiority study. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical evaluation of an evidence-based method based on food characteristics to adjust pancreatic enzyme supplements dose in cystic fibrosis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Prescription patterns of pancreatic enzyme replacement therapy for patients with pancreatic cancer in the United States. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery. [2011]

13. United States pubmed.ncbi.nlm.nih.gov

Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. [2022]