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

Phase 2

Completed

• Conditions: Post-ERCP Acute Pancreatitis
• Interventions: Drug: placebo; Drug: Hemin

• Registration Number: NCT01855841
• Lead Sponsor: Erasme University Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2013-05-08
• Study First Submitted QC: 2013-05-14
• Study First Posted: 2013-05-17
• Primary Completion: 2021-06-01
• Study Completion: 2021-06
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-05
• Last Update Posted: 2021-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 284

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	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
Hemin	Hemin	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

Primary Outcome Measures

Name	Time	Method
Incidence of post-ERCP acute pancreatitis	at day 1 post-ERCP	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.

Secondary Outcome Measures

Name	Time	Method
length of stay	during the hospitalization (up to 2 months)	the length of stay in the hospital will be recorded. if a complication occurs (post-ERCP acute pancreatitis or other, it will be recorded)
safety of hemin administration	within 7 days	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
severity of post-ERCP acute pancreatitis	during the hospital stay (up to 2 months)	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?)

Trial Locations

Locations (6)

Hôpital Ambroise Paré; 🇧🇪 Mons, Belgium

Erasme Hospital, Université Libre de Bruxelles (ULB); 🇧🇪 Brussels, Belgium

CHU Brugmann; 🇧🇪 Brussels, Belgium

Centre Hospitalier de Jolimont-Lobbes; 🇧🇪 Haine-St-Paul, Belgium

ISPPC CHU Vésale; 🇧🇪 Montigny Le tilleul, Belgium

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan