Corticosteroids for Acute Pancreatitis

(CRISP Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Michael W Donnino, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Corticosteroids

Disqualifiers: Autoimmune pancreatitis, Pregnancy, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if giving hydrocortisone can help patients with severe acute pancreatitis by reducing inflammation. The goal is to see if this treatment can improve their health and reduce the time they need to stay in the hospital. Hydrocortisone seems to be effective in treating the early inflammation associated with severe acute pancreatitis.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are already taking corticosteroids at a dose greater than 5mg of oral prednisone daily (or equivalent), you may not be eligible to participate.

What evidence supports the effectiveness of the drug hydrocortisone for treating acute pancreatitis?

Research shows that hydrocortisone can significantly reduce mortality in severe acute pancreatitis by suppressing harmful inflammatory responses. In an experimental study, hydrocortisone treatment reduced the death rate from 86% to 13% in severe cases. ^{1 2 3 4 5}

Is hydrocortisone generally safe for use in humans?

Hydrocortisone has been studied in various animal models for conditions like acute pancreatitis, showing mixed results. While it can reduce mortality in severe cases, it may also exacerbate certain conditions if not administered correctly. Overall, hydrocortisone is generally considered safe in humans when used appropriately, but its effects can vary depending on the specific condition and treatment protocol. ^{1 2 4 5 6}

How does the drug hydrocortisone differ from other treatments for acute pancreatitis?

Hydrocortisone is unique in treating acute pancreatitis because it can reduce inflammation by suppressing the breakdown of arachidonic acid and cytokine production, which are chemicals that cause inflammation. It has shown effectiveness in reducing mortality in severe cases by addressing the early systemic inflammatory response, which is not a standard approach in current treatments for this condition. ^{1 2 3 4 7}

Eligibility Criteria

This trial is for adults over 18 with severe acute pancreatitis, indicated by high lipase levels and a SOFA score ≥3. Participants must be in or heading to intensive care. It's not for those already on >5mg of prednisone (or equivalent), with autoimmune pancreatitis, contraindications to steroids, prisoners, or if pregnant.

Inclusion Criteria

I am 18 years old or older.

I have been diagnosed with severe pancreatitis.

SOFA disease severity score ≥3 (or at least 3 points above a known baseline)

Exclusion Criteria

I have been diagnosed with autoimmune pancreatitis.

I am prescribed more than 5mg of oral prednisone daily.

Pregnancy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intravenous hydrocortisone or placebo every 8 hours for 72 hours

72 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of mortality and quality of life

90 days

Treatment Details

Interventions

• Hydrocortisone (Corticosteroid)

Trial Overview The study tests whether a short course of intravenous hydrocortisone can improve outcomes and reduce hospital stays in patients with severe acute pancreatitis compared to a placebo. Hydrocortisone is an anti-inflammatory drug that may help control the disease's progression.

Participant Groups

Group I: Hydrocortisone Experimental Treatment 1 Intervention

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)

Group II: Placebo Placebo Group 1 Intervention

Patients in this arm will be given matching placebo (50ml 0.9%NACL) by nursing staff every 8 hours for 72 hours (9 administrations)

Hydrocortisone is already approved in European Union, United States, Canada for the following indications:

🇪🇺 Approved in European Union as Hydrocortisone for:

• Adrenal insufficiency
• Allergic reactions
• Asthma
• Severe acute pancreatitis

🇺🇸 Approved in United States as Hydrocortisone for:

• Adrenal insufficiency
• Allergic reactions
• Asthma
• Severe acute pancreatitis

🇨🇦 Approved in Canada as Hydrocortisone for:

• Adrenal insufficiency
• Allergic reactions
• Asthma
• Severe acute pancreatitis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Beth Israel Deaconess Medical Center Boston, MA

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center Lead Sponsor

References

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

Hydrocortisone treatment of early SIRS in acute experimental pancreatitis. [2019] This work studied the effects of hydrocortisone treatment in experimental acute pancreatitis on cytokines, phospholipase A2, and breakdown products of arachidonic acid and survival. Edematous and necrotizing pancreatitis were induced in Wistar rats by cerulein hyperstimulation and retrograde intraductal infusion of sodium taurocholate, respectively. Hydrocortisone (10 mg/kg) was administered intravenously 10 minutes after induction of acute pancreatitis. Serum was assayed for phospholipase A2; interleukin (IL) 1beta, IL-6, IL-10, thromboxane B2; Prostaglandin E2; and leukotriene B4 at five different time points. A significant release of inflammatory mediators was seen only in the severe model. Hydrocortisone powerfully suppressed arachidonic acid breakdown products and only mildly attenuated the systemic increase of phospholipase A2 and pro- and antiinflammatory cytokines. The mortality rate after 72 hr in the severe model was 86%. Hydrocortisone treatment reduced mortality to 13% (P = 0.001; Fisher's exact test). Hydrocortisone seems to be effective in the treatment of the early systemic inflammatory response syndrome associated with severe acute pancreatitis.

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

Effect of chronic administration of hydrocortisone on the induction and evolution of acute pancreatitis induced by cerulein. [2019] The effects of chronic administration of hydrocortisone (10 mg/kg/day) on the development and evolution of acute pancreatitis induced by supramaximal stimulation with cerulein were examined in the rat. In these circumstances the potentially therapeutic effect of L-364,718, a CCK-receptor antagonist, was assayed. Administration of hydrocortisone over 7 days did not increase the severity of edematous acute pancreatitis induced by cerulein, since the reduction in pancreatic secretion, the hyperamylasemia and the increase in the levels of hematocrit and fluid in the pancreatic tissue were similar in rats with acute pancreatitis treated and untreated with hydrocortisone previously. When hydrocortisone was administered chronically, before administration of supramaximal doses of cerulein, a spontaneous regression of acute pancreatitis occurred. However, when hydrocortisone administration was continued after inducing pancreatitis, pancreatic recovery was prevented, observing a significantly depressed acinar secretion and elevated values of hematocrit and tissue fluid (edema). L-364,718 administration proved to be detrimental in the evolution of edematous acute pancreatitis when the rats had been treated chronically with hydrocortisone because the blockade exerted on secretion prevented the draining of enzymes stored in excess by hydrocortisone administration.

3. England pubmed.ncbi.nlm.nih.gov

Vasodilatory shock in severe acute pancreatitis without sepsis: is there any place for hydrocortisone treatment? [2013] Hydrocortisone (HC) has been reported to rapidly improve hemodynamics and reduce the time to vasopressor cessation in septic shock, but none has focused on this effect in acute pancreatitis. We therefore performed a study to assess the effects of hydrocortisone on catecholamine-dependent shock among patients with severe acute pancreatitis.

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

Experimental model of acute pancreatitis in Wistar rat: glucocorticoid treatment profile. [2019] Severe acute pancreatitis may be triggered by an extrapancreatic insult at the peri-Vaterian duodenum such as that occurring in the short-term, 20 min closed duodenal loop model in Wistar rat, which mimics biliary acute pancreatitis or that following endoscopy. Glucocorticoids are immunological modulators whose therapeutic value is worth investigating. Wistar male rats were used under standardized conditions. Acute pancreatitis was induced by instillation of a 7% sodium tauraocholate solution with 5 drops of methylene blue to monitor absence of duodenal bilio pancreatic reflux into the peri-Vaterian duodenum for 20 min. Detection of biliopancreatic reflux with methylene blue was an exclusion criterion. Different doses and times of administration of subcutaneous hydrocortisone were evaluated. Biochemical assays were carried out in blood samples and pancreatic and lung tissue, while histpathological studies were done in the pancreas, lung liver, duodenum, spleen, kidneys, suprarenal glands, and stomach. Animals subjected to the experimental model developed severe acute pancreatitis. According to the dose and time of administration, hydrocortisone therapy was effective and beneficial at a dose of 4 mg/kg give 30 min before inducing acute pancreatitis. It was ineffective when doses were 4 mg/kg and given either before or after. Thus, the proposed model is valid and useful to study the initiation mechanism of acute pancreatitis caused extrapancreatically while its amelioration by glucocorticoid is related the dose and time factor to achieve therapeutical results.

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

Action of CCK on CDE diet-induced acute pancreatitis in rats treated with hydrocortisone. [2019] The present work studies the effect of previous hydrocortisone administration (10 mg/kg/day) over 7 days on the later development of diet-induced acute pancreatitis in the rat. Acute pancreatitis was induced by feeding a diet deficient in choline and supplemented with 0.5% ethionine (CDE diet) over 10 days. Hydrocortisone pretreatment exacerbated CDE-induced acute pancreatitis. There was a significant increase in serum amylase, pancreatic edema, and haematocrit levels and an insignificant decrease in pancreatic mass in rats pretreated with hydrocortisone. Pancreatic enzyme secretion was strongly reduced in the rats subjected to acute pancreatitis, and although the drop in enzyme levels did not reach statistical significance, the values of secretion were even further reduced in the animals treated with hydrocortisone, pointing to the absence of pancreatic functionality. This effect can be attributed to enzyme storage elicited by previous hydrocortisone administration; activated intracellularly, these enzymes could aggravate the pathology. Administration of the cholecystokinin octapeptide (CCK-8) (10 micrograms/kg/day) during the development of acute pancreatitis in animals pretreated with hydrocortisone substantially improved the general state of the animals' pancreases. There was a significant decrease in serum amylase, pancreatic edema and haematocrit levels in rats injected with CCK, which was accompanied by an increase in pancreatic functionality. Conversely, the administration of L-364,718 (0.1 mg/kg/day), a CCK antagonist, did not improve pancreatic functionality and did not appreciably affect the general state of the organ. It is concluded that in rats with storage levels increased by hydrocortisone administration that are subjected to acute pancreatitis, the secretagogue effect of CCK is more beneficial than the repose of the gland induced by L-364,718.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Perioperative Hydrocortisone Reduces Major Complications After Pancreaticoduodenectomy: A Randomized Controlled Trial. [2017] The aim of this study was to study whether post-pancreaticoduodenectomy complications (PPDC) in high-risk patients can be reduced with hydrocortisone.

7. Hungary pubmed.ncbi.nlm.nih.gov

The effects of glucocorticoids and a glucocorticoid antagonist (RU 38486) on experimental acute pancreatitis in rat. [2013] The effects of glucocorticoids on acute pancreatitis are a matter of dispute. In animal experiments, dexamethasone and hydrocortisone significantly decreased the serum amylase activities 8 hours after the induction of pancreatitis. In the dexamethasone treated group, the serum IL-6 level was significantly decreased at 4 and 8 hours, while in the hydrocortisone treated group, all the IL-6 values were significantly diminished vs. the control group. As compared to the control, a glucocorticoid antagonist (RU 38486) did not influence the serum amylase activity, but significantly increased the serum IL-6 level. These results suggest that glucocorticoids may play a role in the control of pancreatitis caused by inhibition of cytokine production.