Hemin to Prevent Post-ERCP (Endoscopic Retrograde Cholangiopancreatography) Acute Pancreatitis

Study Overview
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Brief Summary
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ERCP (endoscopic retrograde cholangiopancreatography) has been largely demonstrated to be effective in multiple bilio-pancreatic indications. However, one of the feared complication of this technique is acute pancreatitis, which happens in 5 to 25% of cases. Some patient groups have been demonstrated to present a higher risk linked to individual factors or to the procedure. Some interventions (endoscopic or pharmacologic) have been evaluated to reduce the incidence of this complication but each has his own inconvenient. Recently, the activation of heme oxygenase (HO) by intraperitoneal administration of hemin has been demonstrated to be effective in prevention and treatment of acute pancreatitis mice models. This protective effect has been associated to intrapancreatic HO-1 positive macrophage recruitment activated by hemin. The investigators thus propose to conduct a prospective randomized double blind controlled trial to demonstrate a protective effect of hemin administration against post-ERCP acute pancreatitis in high risk patients.

Detailed Description
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Patients for who a pancreatic stent placement is indicated will be excluded from the study. The aims of this study are: 1) to study in a pathophysiologic point of view the activation of HO-1 by hemin in human and its protective effect in post-ERCP acute pancreatitis incidence. 2) to use the human situation of post-ERCP acute pancreatitis as early pancreatitis model to study the administration of hemin as treatment of acute pancreatitis in general.

Official Title
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Prevention of Post-ERCP Acute Pancreatitis by Heme-oxygenase Activation Through the Administration of Hemin : a Prospective, Randomized Double Blind Controlled Trial

Conditions
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Post-ERCP Acute Pancreatitis

Intervention / Treatment
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* Drug: Hemin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: one or more factors of >10% post-ERCP acute pancreatitis risk: former episode of acute pancreatitis former episode of post-ERCP acute pancreatitis normal bilirubin level main pancreatic duct injection endoscopic biliary sphincteroplasty (balloon dilation of biliary sphincter) precut papillotomy pancreatic sphincterotomy Exclusion Criteria: patient for whom a pancreatic stent is inserted (Sphincter of Oddi dysfunction, ampullectomy) ongoing acute pancreatitis chronic pancreatitis (Cremer classification >=2) age < 18 y/o pregnancy hemin allergy severe renal failure (MDRD<30ml/min/1.73m2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hemin<br>A peripheral perfusion of 4mg/kg of hemin (Normosang) diluted in 100mL NaCL (sodium chloride) 0.9% will be administered in 30-60minutes as soon as possible after the end of the ERCP, followed by 100mL of NacL 0.9% to flush the vein | Drug: Hemin<br>* A single perfusion of 4mg/kg hemin diluted in 100mL of NaCl 0.9% administered as soon as possible after the end of the ERCP followed by 100mL of NaCL 0.9% to flush the vein<br>* Other names: Normosang;|
| Placebo Comparator: Placebo<br>The same amount of NaCl 0.9% (100 ML followed by a flushing perfusion of 100mL) will be perfused to the patient as soon as possible after the end of the ERCP | Drug: placebo<br>* A single perfusion of 100mL of NaCl 0.9% administered as soon as possible after the end of the ERCP followed by 100mL of NaCL 0.9% to flush the vein<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of post-ERCP acute pancreatitis | Post-ERCP acute pancreatitis is defined by an abdominal pain compatible with pancreatitis and the elevation of seric lipases more than 3 times the upper limit of normal on days 1 post-ERCP. | at day 1 post-ERCP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| severity of post-ERCP acute pancreatitis | If post-ERCP acute pancreatitis happens, all parameters of severity will be recorded (clinical, biological, intra-abdominal collections seen on abdominal scanner/magnetic resonance, organ failure, need for ICU hospitalization, need for further treatment: surgery/endoscopy/radiological drainage?) | during the hospital stay (up to 2 months) | 
| length of stay | the length of stay in the hospital will be recorded. if a complication occurs (post-ERCP acute pancreatitis or other, it will be recorded) | during the hospitalization (up to 2 months) | 
| safety of hemin administration | Few side effects of hemin are known (headache, superficial thrombophlebitis in the perfused vein); they will be recorded as well as other unexplained clinico-biological events | within 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ERCP, virgin papilla, risk of post-ERCP acute pancreatitis