Corticosteroids to Treat Pancreatitis (CRISP)

Corticosteroids to Reduce Inflammation in Severe Pancreatitis: A Randomized, Controlled Study

This research is being done to determine if the administration of a short course of intravenous hydrocortisone, an anti-inflammatory medication, to patients with severe acute pancreatitis will improve their clinical outcomes and decrease the length of hospitalization. We think that because inflammation in the body drives the progression of pancreatitis, giving a short course of intravenous hydrocortisone may mitigate disease progression and improve clinical outcomes in patients with severe acute pancreatitis.

Study Overview

• Status: Recruiting
• Conditions: Pancreatitis; Pancreatitis, Acute; Corticosteroid; Hydrocortisone
• Intervention / Treatment: Drug: Hydrocortisone; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous hydrocortisone on clinical outcomes in patients with severe acute pancreatitis. The interventional drug is Hydrocortisone (100 mg of hydrocortisone in 50 milliliters of saline solution). The placebo is saline and is identical in appearance and volume to the interventional drug. Study drug will be administered intravenously every 8 hours for 72 hours as per standard clinical procedures by nursing staff. The patient's sequential organ failure assessment score (SOFA) will be assessed for changes over time. Blood will be drawn at several time points to assess biomarkers over time.

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Donnino, MD; Phone Number: 6177542295; Email: mdonnino@bidmc.harvard.edu
• Study Contact Backup: Name: Katherine Berg, MD; Email: kberg@bidmc.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Jeremy Silverman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult (≥18 years)
2. Acute pancreatitis as defined by a clinical diagnosis of pancreatitis and a lipase level ≥3x the upper limit of normal.
3. Admission or planned admission to an intensive care unit
4. SOFA disease severity score ≥3 (or at least 3 points above a known baseline)

Exclusion Criteria:

1. Known diagnosis of autoimmune pancreatitis
2. Existing clinical indication for corticosteroids at a dose >5mg of oral prednisone daily (or equivalent)
3. Contraindication to receiving corticosteroids
4. Protected populations (prisoners)
5. Pregnancy

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: Hydrocortisone; Patients in this arm will be administered 100 mg of hydrocortisone in 50 milliliters of saline solution by nursing staff every 8 hours for 72 hours as per standard clinical procedures (9 administrations)	Drug: Hydrocortisone; Hydrocortisone is a steroid (corticosteroid) medication.; Other Names: Cortef; Cortisol; Hydrocort
Placebo Comparator: Placebo; Patients in this arm will be given matching placebo (50ml 0.9%NACL) by nursing staff every 8 hours for 72 hours (9 administrations)	Drug: Placebo; 50ml of 0.9% NACL will serve as the placebo; Other Names: Normal Saline; 0.9% NACL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Illness Measure	Change in Sequential Organ failure Assessment (SOFA) Score over 72 hours	Enrollment to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Failure Measure	Progression to Acute Respiratory Distress Syndrome (ARDS) assessed as a dichotomous variable for those patients without ARDS upon enrollment	Enrollment to 28 days [truncated at 28 days]
Alive and Ventilator Free Days	Number of days during the 28-day period after enrollment in which the patient is alive and does not receive mechanical ventilation	Enrollment to 28 days [truncated at 28 days]
Long-term Functional/Quality of Life Measure	Scores from Short Form 36 (SF36), a validated survey used measure health-related quality of life, with higher scores indicating better quality of life.	90 days after Enrollment
In-hospital mortality	Dichotomous variable that assesses whether or not the patient expired prior to hospital discharge	Enrollment to 90 days [truncated at 90 days]
28-day mortality	Dichotomous variable that indicates whether or not patient expired by the 28-day time-point while enrolled in the trial.	Enrollment to 28 days [truncated at 28 days]
90-day mortality	Dichotomous variable that indicates whether or not patient expired by the 90-day time-point while enrolled in the trial.	Enrollment to 90 days [truncated at 90 days]
Alive and Hospital free days	Number of days in which the patient was alive and not in the hospital.	Enrollment to 28 days [truncated at 28 days]
Severity of Illness Measure Stratified By Predicted Survival (Physician Opinion)	Sequential Organ failure Assessment (SOFA) Score over 72 hours compared for patients stratified by survival likelihood per physician opinion into three subgroups (likely, unlikely, or uncertain)	Enrollment to 72 hours
Severity of Illness Measure Stratified By Bedside Index of Severity in Acute Pancreatitis (BISAP) score	Sequential Organ failure Assessment (SOFA) Score over 72 hours compared for patients stratified by BISAP scores into two groups (BISAP ≥3; BISAP < 3)	Enrollment to 72 hours

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Michael Donnino, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Grossestreuer AV, Moskowitz A, Andersen LW, Holmberg MJ, Konacki V, Berg KM, Chase M, Cocchi MN, Donnino MW. Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis. Crit Care Explor. 2020 Nov 23;2(12):e0270. doi: 10.1097/CCE.0000000000000270. eCollection 2020 Dec.
• Moskowitz A, Huang DT, Hou PC, Gong J, Doshi PB, Grossestreuer AV, Andersen LW, Ngo L, Sherwin RL, Berg KM, Chase M, Cocchi MN, McCannon JB, Hershey M, Hilewitz A, Korotun M, Becker LB, Otero RM, Uduman J, Sen A, Donnino MW; ACTS Clinical Trial Investigators. Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial. JAMA. 2020 Aug 18;324(7):642-650. doi: 10.1001/jama.2020.11946.
• Donnino MW, Andersen LW, Berg KM, Chase M, Sherwin R, Smithline H, Carney E, Ngo L, Patel PV, Liu X, Cutlip D, Zimetbaum P, Cocchi MN; Collaborating Authors from the Beth Israel Deaconess Medical Center's Center for Resuscitation Science Research Group. Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial. Crit Care. 2016 Apr 3;20:82. doi: 10.1186/s13054-016-1257-x.
• Vine J, Berlin N, Moskowitz A, Berg KM, Liu X, Balaji L, Donnino MW, Grossestreuer AV. Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomized, placebo controlled clinical trial. Contemp Clin Trials. 2024 Apr;139:107486. doi: 10.1016/j.cct.2024.107486. Epub 2024 Feb 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Bedside index of severity in acute pancreatitis; Sequential Organ Failure Assessment
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pharmaceutical Preparations; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Hydrocortisone; Saline Solution
• Other Study ID Numbers: 2021P-000803

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes