WithdrawnPhase 4

Thiopurine Induced Pancreatitis in IBD Patients

Stopped: No Participants Enrolled

Israel0Started 2015-03

Plain-language summary

Azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP) were developed over 50 years ago by Gertrude Elion and George Hitchings and were initially used clinically in the management of childhood leukemia and organ transplantation. The first case report of 6-MP use in inflammatory bowel disease (IBD) was from 1962 , and since then the use of thiopurines has been well established in the management of moderate to severe IBD. Thiopurines offer an inexpensive and effective treatment option for maintenance of remission of IBD in comparison to biological agents which may be 30 times more expensive . Although 50-60% of IBD patients respond to thiopurines, a significant proportion of patients will not tolerate them due to various adverse effects . The adverse effects of thiopurines may be dose related, patient related or idiosyncratic. The immunosuppressive effects of thiopurines also increase the rates of opportunistic infections. Thiopurines are also associated with a higher rate of malignancies, particularly a malignant Burkitt-like lymphoma, related to Epstein-Barr virus infection . Other adverse effects of thiopurine relate to allergic phenomenon. An idiosyncratic adverse effect of thiopurine use is acute pancreatitis (AP). Acute inflammation of the pancreas defined by INSPPIRE criteria: requiring 2 of: 1. Abdominal pain compatible with AP 2. Serum amylase and/or lipase ≥ 3 times upper limits of normal 3. Imaging findings of AP Drug induced AP is the assumed diagnosis when no other cause of AP can be found, the patient is taking a drug known to be associated with AP, and symptoms resolve after drug discontinuation. If pancreatitis re-occurs on re-exposure, the drug is definitely considered the cause. While drugs are considered a rare cause of AP and most cases are mild and self limited , there is an 8 fold higher risk of AP in IBD patients treated with AZA . Thiopurine induced AP is usually detected within 4 weeks of starting treatment. However in the case of thiopurine induced AP, there has been no clear understanding of the mechanism. Thiopurine induced AP is generally considered an indication to cease thiopurine therapy, due to the assumed risk of recurrence of AP on reintroduction. There exists several case reports and anecdotal evidence that reintroducing thiopurines following an assumed thiopurine associated AP can be well tolerated. The investigators hypothesize that AZA and/or 6-MP can be safely reintroduced in the management of IBD patients following thiopurine-induced pancreatitis. If in the past the patients were treated with AZA, they will now be commenced on 6-MP, and if in the past they were treated with 6-MP, they will be commenced on AZA.

Who can participate

Age range

5 Years – 60 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Patients diagnosed with IBD, treated previously with thiopurines, and ceased treatment due to suspected thiopurine-induced pancreatitis * Ability to consent to and participate in the study and follow study procedures * Age 5-60 years Exclusion Criteria: * Previous severe pancreatitis requiring prolonged hospital admission or intensive care involvement, or Ranson's criteria ≥ 3 * No clinical need to reintroduce a thiopurine for management of IBD at the time of the study (e.g. stable on another medication, or mild phenotype of disease), based on clinical assessment of treating gastroenterologist * Diagnosis of recurrent pancreatitis syndrome * Diabetes mellitus or any other neuropathy which may dampen the clinical presentation of pancreatitis * Known or suspected allergy or intolerance to thiopurines, besides previous pancreatitis * Any other laboratory or clinical condition that the investigator considers clinically significant that could impact the outcome of the study or the safety of the patient.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Number of participants demonstrating biochemical or clinical evidence of pancreatitis

Timeframe: 3 month period following intervention

Trial details

NCT IDNCT02281799

SponsorShaare Zedek Medical Center

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2018-01

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