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

Post-ERCP Acute Pancreatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01855841
• Other study ID #: Hemin_AP
• Status: Completed
• Phase: Phase 2
• Start date: April 2012
• Est. completion date: June 2021

Study information

• Verified date: July 2021
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 284
• Est. completion date: June 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Pancreatitis
• Post-ERCP Acute Pancreatitis

Intervention

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
• 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

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels
Belgium	Erasme Hospital, Université Libre de Bruxelles (ULB)	Brussels
Belgium	Centre Hospitalier de Jolimont-Lobbes	Haine-St-Paul
Belgium	Hôpital Ambroise Paré	Mons
Belgium	ISPPC CHU Vésale	Montigny Le tilleul
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Erasme University Hospital

Countries where clinical trial is conducted

Belgium,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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)
Secondary	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)
Secondary	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