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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a short course of hydrocortisone, an anti-inflammatory drug, can help people with severe acute pancreatitis recover faster and reduce their hospital stay. Pancreatitis, a painful condition involving inflammation of the pancreas, may benefit from hydrocortisone's ability to reduce inflammation. The trial includes two groups: one receiving hydrocortisone and the other a placebo (a treatment with no active drug). It is suitable for those diagnosed with acute pancreatitis who are in or about to enter intensive care. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that hydrocortisone is likely to be safe for humans?

Research has shown mixed safety results for using hydrocortisone in severe acute pancreatitis. Some animal studies suggest that hydrocortisone can help by reducing pancreatic inflammation, potentially improving survival rates. However, other research has raised safety concerns, noting a higher risk of death with high doses of hydrocortisone.

Hydrocortisone is already used for other health issues, indicating general safety for people. Still, for acute pancreatitis, the safety information remains unclear, necessitating further research. This trial is in an early stage and aims to better understand the safety and effectiveness of hydrocortisone for this specific condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using hydrocortisone for acute pancreatitis because it offers a novel approach to reduce inflammation quickly. Unlike traditional treatments that often focus on managing symptoms and supporting organ function, hydrocortisone works by directly targeting the inflammation at the core of the condition. This corticosteroid might provide faster relief by calming the immune response in just a few days, which could significantly improve patient outcomes and reduce hospital stays compared to current care strategies.

What evidence suggests that hydrocortisone might be an effective treatment for acute pancreatitis?

Research has shown that hydrocortisone might help treat severe acute pancreatitis by reducing swelling. In this trial, some participants will receive hydrocortisone, which studies have linked to shorter hospital stays, fewer surgeries, and lower death rates. One study showed that hydrocortisone significantly reduced death rates from 86% to 13% in a severe pancreatitis model. In animal studies, hydrocortisone improved survival rates and lessened damage to the pancreas. These findings suggest that hydrocortisone could help manage swelling and improve outcomes for patients with severe acute pancreatitis. ^{1 2 5 6 7}

Who Is on the Research Team?

Michael W Donnino, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4555660/

Corticosteroid therapy for severe acute pancreatitis: a meta ... Corticosteroid therapy for SAP was associated with reductions in the length of hospital stay, the need for surgical intervention, and the mortality rate.

2. e-century.us e-century.us/files/ijcep/8/7/ijcep0007864.pdf

Corticosteroid therapy for severe acute pancreatitis: a meta ... When administered shortly before endo- toxin, hydrocortisone greatly reduced the clini- cal response to endotoxin in normal volunteers. [21]. This interaction ...

3. withpower.com withpower.com/trial/phase-2-pancreatitis-3-2022-21edb

Corticosteroids for Acute Pancreatitis (CRISP Trial) In a study involving Wistar rats with induced acute pancreatitis, hydrocortisone treatment significantly reduced mortality from 86% to 13% within 72 hours, ...

4. researchgate.net researchgate.net/publication/11671555_Hydrocortisone_Treatment_of_Early_SIRS_in_Acute_Experimental_Pancreatitis

Hydrocortisone Treatment of Early SIRS in Acute ... 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).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4128976/

Efficacy of glucocorticoids in rodents of severe acute ... Our results showed that corticosteroid is effective at reducing pancreatic ascites production and histopathological score of pancreas and improving survival in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04469686

NCT04469686 | Phase 3 Study to Evaluate the Safety and ... Phase 3 Study to Evaluate the Safety and Efficacy of Hydrocortisone Acetate Suppositories ... Acute or chronic pancreatitis at the time of enrollment.

7. news.ki.se news.ki.se/cortisone-can-increase-risk-of-acute-pancreatitis

Cortisone can increase risk of acute pancreatitis The results show that people treated with cortisone in tablet form ran a 70 per cent higher risk of developing acute pancreatitis.