Corticosteroids for Acute Pancreatitis

(CRISP Trial)

Overseen By Katherine Berg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Corticosteroids

Disqualifiers: Autoimmune pancreatitis, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 72 hours

86 Participants Needed

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}

Research Team

Michael W Donnino, MD

Principal Investigator

Beth Israel Deaconess Medical Center

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 have been diagnosed with severe pancreatitis.

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

I am currently in or expected to be in intensive care.

Exclusion Criteria

I have been diagnosed with autoimmune pancreatitis.

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

Pregnancy

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

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

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Findings from Research

In a study involving Wistar rats with induced acute pancreatitis, hydrocortisone treatment significantly reduced mortality from 86% to 13% within 72 hours, indicating its potential efficacy in severe cases.

Hydrocortisone effectively suppressed the breakdown products of arachidonic acid and had a mild effect on inflammatory cytokines, suggesting it may help manage the systemic inflammatory response associated with severe acute pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocortisone treatment of early SIRS in acute experimental pancreatitis. Gloor, B., Uhl, W., Tcholakov, O., et al.[2019]

Chronic administration of hydrocortisone (10 mg/kg/day) for 7 days did not worsen the severity of acute pancreatitis induced by cerulein in rats, indicating that it does not exacerbate the condition.

However, while hydrocortisone treatment before pancreatitis led to spontaneous recovery, continuing hydrocortisone after the onset of pancreatitis hindered recovery, resulting in increased pancreatic edema and reduced enzyme secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chronic administration of hydrocortisone on the induction and evolution of acute pancreatitis induced by cerulein. Pescador, R., Manso, MA., Rebollo, AJ., et al.[2019]

In a study of 10 patients with severe acute pancreatitis treated with hydrocortisone, the time to wean off norepinephrine was significantly shorter (61 hours) compared to 141 hours in the control group, indicating hydrocortisone may help stabilize blood pressure more quickly.

Patients receiving hydrocortisone also required less norepinephrine overall, suggesting that low doses of hydrocortisone can effectively reduce the need for vasopressor support in catecholamine-dependent shock associated with severe acute pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasodilatory shock in severe acute pancreatitis without sepsis: is there any place for hydrocortisone treatment? Eklund, A., Leppäniemi, A., Kemppainen, E., et al.[2013]

In a study using Wistar rats, severe acute pancreatitis was successfully induced, providing a valid model to investigate the condition's mechanisms and potential treatments.

Hydrocortisone was found to be effective in reducing the severity of pancreatitis when administered at a dose of 4 mg/kg, 30 minutes before the induction of the condition, while lower or higher doses were ineffective or harmful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental model of acute pancreatitis in Wistar rat: glucocorticoid treatment profile. Cosen-Binker, LI., Binker, MG., Negri, G., et al.[2019]

Hydrocortisone pretreatment in rats exacerbated diet-induced acute pancreatitis, leading to increased serum amylase, pancreatic edema, and reduced pancreatic functionality, indicating that hydrocortisone may worsen the condition.

The administration of cholecystokinin octapeptide (CCK-8) during acute pancreatitis significantly improved pancreatic health and functionality in hydrocortisone-pretreated rats, while a CCK antagonist did not provide similar benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Action of CCK on CDE diet-induced acute pancreatitis in rats treated with hydrocortisone. Manso, MA., Rebollo, A., Pescador, R., et al.[2019]

In a randomized controlled trial involving 155 patients undergoing pancreaticoduodenectomy, hydrocortisone treatment significantly reduced overall complications in high-risk patients (18% vs 41% with placebo; P < 0.05).

While hydrocortisone did not affect urine trypsinogen release, it showed trends towards lower rates of clinically significant postoperative pancreatic fistulas (11% vs 27%), postpancreatectomy hemorrhage (14% vs 24%), and delayed gastric emptying (29% vs 44%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Hydrocortisone Reduces Major Complications After Pancreaticoduodenectomy: A Randomized Controlled Trial. Laaninen, M., Sand, J., Nordback, I., et al.[2017]

In animal studies, glucocorticoids like dexamethasone and hydrocortisone significantly reduced serum amylase levels and IL-6 cytokine levels after inducing pancreatitis, indicating their potential efficacy in managing this condition.

The use of a glucocorticoid antagonist increased IL-6 levels without affecting serum amylase, suggesting that glucocorticoids may help control pancreatitis by inhibiting harmful cytokine production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of glucocorticoids and a glucocorticoid antagonist (RU 38486) on experimental acute pancreatitis in rat. Lázár, G., Varga, J., Lázár, G., et al.[2013]

References

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

Hydrocortisone treatment of early SIRS in acute experimental pancreatitis. [2019]

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]

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

Vasodilatory shock in severe acute pancreatitis without sepsis: is there any place for hydrocortisone treatment? [2013]

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

Experimental model of acute pancreatitis in Wistar rat: glucocorticoid treatment profile. [2019]

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

Action of CCK on CDE diet-induced acute pancreatitis in rats treated with hydrocortisone. [2019]

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

Perioperative Hydrocortisone Reduces Major Complications After Pancreaticoduodenectomy: A Randomized Controlled Trial. [2017]

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

The effects of glucocorticoids and a glucocorticoid antagonist (RU 38486) on experimental acute pancreatitis in rat. [2013]