Pancreatic Enzyme Replacement in Acute Necrotizing Pancreatitis (PERiANP)

Effect of Pancreatic Enzyme Replacement Therapy in Patients With Acute Necrotizing Pancreatitis: A Multicenter Double Blinded Randomised Placebo Controlled Trial

In this multicenter, double blinded, placebo-controlled, 1:1 parallel group RCT, the investigators propose to evaluate the impact of pancreatic exocrine replacement therapy on patients with acute necrotizing pancreatitis (ANP). The investigators will include patients of 18-60yrs age and both genders with >50% pancreatic parenchymal necrosis and at least 5% loss of body weight.

The primary outcome measure is percent change in body weight at 3 months after enrolment. The intervention will include pancreatic enzyme consisting of 25000 IU of lipase and similar appearing placebo.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Exocrine Insufficiency; Acute Necrotizing Pancreatitis
• Intervention / Treatment: Drug: Placebo; Drug: Pancreatic enzyme capsules

Detailed Description

Acute pancreatitis (AP), an inflammatory disorder of the pancreas, is mild and self-limiting in most patients. Around 10-20% of AP patients develop acute necrotizing pancreatitis (ANP) which is characterized by destruction of both pancreatic and peripancreatic tissue and is associated with high rate of morbidity and mortality due to both local and systemic complications.

Early recognition and close monitoring of affected patients is crucial. Treatment consists of goal-directed intravenous fluid resuscitation, pain control, and enteral nutrition as early as possible. While sterile necrosis might resolve with above conservative measures, infected necrosis requires antibiotics and further interventions such as percutaneous drainage, minimally invasive surgeries, and endoscopic necrosectomy.

In ANP patients there is direct destruction of acinar tissue that results in pancreatic exocrine insufficiency (PEI). In PEI there is insufficient secretion of pancreatic enzymes that causes inadequate nutrient digestion and absorption resulting in weight loss, malnutrition, metabolic bone disease and fat-soluble vitamins and mineral deficiencies. The risk of PEI after ANP is about 25% over 3 years. According to two meta-analysis, PEI was found to be more prevalent during the index AP episode and it remained persistent in about half of the study population at follow-ups. They also reported that the risk of developing PEI is more in those with alcoholic etiology and severe and necrotizing pancreatitis. Hence, management of PEI following ANP is important to improve nutritional status and quality of life. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for PEI. While the use of PERT is well-established in chronic pancreatitis, its efficacy in patients with ANP is still unclear. Hence, in this study, the investigators aim to provide insights into the potential benefits of enzyme supplementation in patients with ANP by evaluating nutritional status, clinical outcomes, and quality of life.

This is a multicenter, double blinded, placebo-controlled, 1:1 parallel group RCT, the investigators propose to evaluate the impact of pancreatic exocrine replacement therapy on patients with acute necrotizing pancreatitis (ANP). The investigators will include patients of 18-60yrs age and both genders with >50% pancreatic parenchymal necrosis and at least 5% loss of body weight.

The primary outcome measure is percent change in body weight at 3 months after enrolment. The intervention will include pancreatic enzyme consisting of 25000 IU of lipase and similar appearing placebo.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Abdul Rasheed, PharmD; Phone Number: +919652104726; Email: abdulrasheedmd1223@gmail.com

Study Locations

• India
  • Assam
    • Guwahati, Assam, India, 781032
      • Recruiting
      • Gauhati Medical College
      • Contact: Mallika Bhattacharyya, MD; Phone Number: +918135848141; Email: mallikabhattacharyya@gmail.com
  • Telangana
    • Hyderabad, Telangana, India, 500032
      • Recruiting
      • Asian Institute of Gastroenterology Hospitals, Gachibowli
      • Contact: Rupjyoti Talukdar, MD; Phone Number: +917032804231; Email: rup_talukdar@yahoo.com
    • Hyderabad, Telangana, India, 500082
      • Recruiting
      • Asian Institute of Gastroenterology, Banjara Hills
      • Contact: Jahangeer Basha, DM; Phone Number: 9000199577; Email: dr.jahangeer@aighospitals.com
  • West Bengal
    • Kolkata, West Bengal, India, 700080
      • Recruiting
      • ILS Hospital, Dum Dum
      • Contact: Sanjay Banerjee, DM; Phone Number: +919830129866; Email: drsanjaygastro@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with AP according to the Revised Atlanta Classification diagnostic criteria
• Index episode of acute pancreatitis with more than 50% pancreatic parenchymal necrosis and at least 5% loss of pre pancreatitis body weight at the time of screening
• Within 6 weeks of onset of disease
• Able to take food orally
• Age 18-60 years
• Both genders

Exclusion Criteria:

• Underlying chronic pancreatitis
• Recurrent acute pancreatitis
• Pancreatic cancer
• Patients being discharged with NJ tubes
• Pregnancy and lactation
• Inability to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enteric coated enzyme preparation containing: Lipase 25000U, Amylase 18000U, Protease 1000U. These m	Drug: Pancreatic enzyme capsules; Enteric coated pancreatic enzyme
Placebo Comparator: Similar appearing glucose capsules will be provided three times a day along with food; Drug: Placebo Similar appearing glucose capsules	Drug: Placebo; Similar appearing glucose capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in body weight	Body weight (in kg) will be measured at baseline and again at 3 months follow-up, and the difference between the two time points will be used to assess the effect of the intervention on patients' weight status. The change will be expressed as percent change of weight 3 months compared to baseline weight.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Readmission after onset of treatment	Readmission to hospital	3 months
Change in quality of life	Quality of life will be assessed by the Short Form (SF)-36 tool. This is a standardised and validated questionnaire based scoring tool that contains 36 questions dealing with 8 domains of quality of life. The lowest score in this tool is 0 and the highest score is 100, a higher score indicating better quality of life.	3 months
Change in pancreatic exocrine function	Exocrine function will be assessed by the Fecal elastase test and will be expressed as microgram of elastase per gram of stool. Higher value indicates better exocrine function. The cut-off value that will be used is 200mcg/gm elastase, below which exocrine insufficiency will be considered to be present.	3 months
Change in nutritional status: Subjective Global Assesment (SGA)	This is a semiquantitative questionnaire based nutritional assessment tool which classifies the nutritional status as SGA A (normal nutrition), SGA B (mild/moderate malnutrition) and SGC C (severe malnutrition)	3 months
Change in nuritional status: Anthropometry	Skin fold thickness (in mm) over the triceps muscle at the mid arm level.	3 months
Change in nutritional change: Anthropometry	Mid-arm circumference (MAC) in cm.	3 months
Change in nutritional status: Anthropometry	Mid-upper arm muscle circumference (MAMC) in cm.	3 months
Change in nutritional status: Anthropomentry	Mid-arm muscle area (MAMA) in cm square.	3 months
Change in nutritional status: Biochemical assessment	Hemoglobin in gm/dL	3 months
Change in nutritional status: Biochemical assessment	Serum prealbumin in mg/dL	3 months
Change in nutritional status: Biochemical assessment	Vitamin D	3 months
Change in nutritional status: Biochemical assessment	Vitamin B12	3 months
Change in the endocrine status	Fasting blood glucose (FBS)	3 months
Change in the endocrine status	HbA1c	3 months
Change in the endocrine status	Stimulated C-peptide	3 months
Change in patient's impression of change after treatment	This will be evaluated using the Patient's Global Impression of Change (PGIC). The score ranges from 1-7, with a score of 1 indicating very much improved and 7 indicating very much worse	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body composition (Bioimpedence analysis): Body fat mass (kg)	Total body fat will be assessed using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body. The normal range is 10-20kg.	3 months
Change in body composition (Bioimpedence analysis): Skeletal muscle mass (kg)	Skeletal muscle mass will be assessed using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body.	3 months
Change in body composition (Bioimpedence analysis): Total body water (litres)	Total body water will be quantified using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body.	3 months
Change in body composition (Bioimpedence analysis): Phase angle at 50kH (degrees)	Cell membrane integrity will be assessed using the phase angle function of Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body.	3 months
Change in body composition (Bioimpedence analysis): Visceral fat level (numerical unit; normal range (1-12).	Visceral fat level will be assessed using Bioimpedence analysis (BIA) This is a non-invasive method that operates by sending a low-level, imperceptible electrical current through the body. The normal range is from 1-12, a loser value indicating lower visceral fat and higher value indicates larger visceral fat.	3 months

Collaborators and Investigators

• Sponsor: Asian Institute of Gastroenterology, India
• Investigators: Study Director: Rupjyoti Talukdar, MD, Asian Institute of Gastroenterology Hospitals

Publications and helpful links

General Publications

• Wang GJ, Gao CF, Wei D, Wang C, Ding SQ. Acute pancreatitis: etiology and common pathogenesis. World J Gastroenterol. 2009 Mar 28;15(12):1427-30. doi: 10.3748/wjg.15.1427.
• Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.
• Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol. 2019 Aug;16(8):479-496. doi: 10.1038/s41575-019-0158-2.
• Umapathy C, Raina A, Saligram S, Tang G, Papachristou GI, Rabinovitz M, Chennat J, Zeh H, Zureikat AH, Hogg ME, Lee KK, Saul MI, Whitcomb DC, Slivka A, Yadav D. Natural History After Acute Necrotizing Pancreatitis: a Large US Tertiary Care Experience. J Gastrointest Surg. 2016 Nov;20(11):1844-1853. doi: 10.1007/s11605-016-3264-2. Epub 2016 Sep 12.
• Huang W, de la Iglesia-Garcia D, Baston-Rey I, Calvino-Suarez C, Larino-Noia J, Iglesias-Garcia J, Shi N, Zhang X, Cai W, Deng L, Moore D, Singh VK, Xia Q, Windsor JA, Dominguez-Munoz JE, Sutton R. Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis. Dig Dis Sci. 2019 Jul;64(7):1985-2005. doi: 10.1007/s10620-019-05568-9. Epub 2019 Jun 4.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: February 15, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: acute pancreatitis; pancreatic enzyme replacement therapy; pancrearic exocrine insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Acute Necrotizing; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: PERiANP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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