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

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

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.

Study Overview

• Status: Completed
• Conditions: Post-ERCP Acute Pancreatitis
• Intervention / Treatment: Drug: Hemin; Drug: placebo

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 Type: Interventional
• Enrollment (Actual): 284
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • CHU Brugmann
  • Brussels, Belgium, 1070
    • Erasme Hospital, Université Libre de Bruxelles (ULB)
  • Haine-St-Paul, Belgium, 7100
    • Centre Hospitalier de Jolimont-Lobbes
  • Mons, Belgium, 7000
    • Hopital Ambroise Pare
  • Montigny Le tilleul, Belgium, 6110
    • ISPPC CHU Vésale
• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: Hemin; 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; Other Names: Haemin; Normosang
Placebo Comparator: 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	Drug: placebo; 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; Other Names: saline

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with post-ERCP acute pancreatitis and adverse event at interim analysis	After having randomized 50 patients by arm, an interim analysis will be conducted to evaluate the safety (superficial venous thrombophlebitis, headache, unexpected adverse events)and need to complete the study (depending on the results on post-ERCP acute pancreatitis incidence)	after 100 patients

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Investigators: Principal Investigator: Arnaud Lemmers, MD,PhD, Erasme Hospital, Université libre de Bruxelles (ULB), Brussels, Belgium; Study Chair: Jacques Devière, MD, PhD, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Blegium

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: May 8, 2013
• First Submitted That Met QC Criteria: May 14, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: ERCP; virgin papilla; risk of post-ERCP acute pancreatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis
• Other Study ID Numbers: Hemin_AP