Safety and Tolerability of Pirfenidone in Acute Pancreatitis

Eligibility Criteria

• 1. Patients 18 - 85 years of age
• 2. Admitted to hospital for AP, defined by at least 2 of the following 3:
• 1. amylase or lipase values, or both, that are greater than 3 times the upper limit of normal values
• 2. characteristic cross-sectional imaging
• 3. typical upper abdominal pain- acute onset of a persistent, severe, epigastric pain often radiating to the back
• 3. Patients identified, approached, and consented to administer study medication or placebo within 48 hours of diagnosis of AP.
• 4. Predicted to have MSAP or SAP by presence of one or more of the following criteria
• 1. APACHE II ≥ 8
• 2. Modified Glasgow or Imrie score ≥ 3
• 3. CRP \> 150 mg/dL
• 4. PASS score \> 140 at or within 48 hrs. of admission
• 5. CT or MRI imaging suggesting pancreatic and/or peri-pancreatic necrosis
• 1. Age \< 18 or \> 85 years
• 2. Body weight \> 200 kg
• 3. Presentation to the medical attention \> 48 h after diagnosis of AP
• 4. Inability to recruit, randomize and start the allocated treatment within 48h of start of pain
• 5. Ongoing AP or diagnosis of AP in previous 30 days
• 6. Chronic pancreatitis
• 7. Known hypersensitivity to pirfenidone
• 8. AST/ALT ≥ 2 times the upper normal limit.
• 9. Alkaline phosphatase ≥ 2 times the upper normal limit
• 10. Bilirubin higher than upper normal limit
• 11. Moderate to severe heart failure and/or coronary heart disease (New York Heart Association (NYHA) Functional Class III/IV)
• 12. On home oxygen or home mechanical ventilation
• 13. Advanced liver disease
• 14. Paralytic ileus or significant nausea and vomiting
• 15. Chronic Diarrhea
• 16. Immunosuppressive disorder or on immunosuppressive medications
• 17. Active or advanced malignancy
• 18. Known cancer that is end-stage with ongoing palliative care or for which palliative care is appropriate
• 19. Known established infection prior to the onset of acute pancreatitis
• 20. Known history of infective hepatitis
• 21. Known live vaccines or therapeutic infectious agents within one month of admission
• 22. Known pregnancy or lactation at the time of admission
• 23. Ongoing photosensitivity and rash
• 24. Women of childbearing potential who are not on oral or injectable contraceptives or IUDs and do not consent to practice abstinence for period of 4 weeks.
• 25. Known to be currently participating in a trial testing any investigational medicinal product or participation in a clinical study involving a medicinal product in the last three months
• 26. Alcohol or substance abuse in the past 2 years
• 27. Family or personal history of long QT syndrome ( \> 500 msec)
• 28. Medications like fluvoxamine or sildanefil
• 29. Significant photosensitivity or new rash
• 30. Renal disease with GFR \< 30
• 31. Any condition other than above that, in the opinion of the investigator, is likely to result in the death of the patient within the next 2 years
• 32. Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone