Contact information
Type
Scientific
Primary contact
Dr M J Bruno
ORCID ID
Contact details
Academical Medical Centre
Department of Gastroenterology-Hepatology (MDL)
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
m.j.bruno@amc.uva.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
CNI study
Study hypothesis
Acute pancreatitis can be due to many causes including biliary stone disease, alcohol abuse, and medication. It can also be caused by medical intervention through manipulation of area of the ampulla of Vater and diagnostic and/or therapeutic interventions in the biliary and pancreatic ductal system (endoscopic retrograde cholangiopancreaticography [ERCP]).
The overall reported incidence of post-ERCP pancreatitis is 7%, in certain subgroups with an increased risk this goes up to 20%. Local damage (temporary increased ductal pressure due to contrast injection and/or oedema due to manipulations) is followed by a local inflammatory response (Tumour Necrotising Factor [TNF], Interleukin-one [IL-1], Interleukin-six [IL-6]). In 80% of cases post-ERCP pancreatitis runs a relatively benign course with a few day of (severe) abdominal pain and an uneventful recovery. In other cases a severe pancreatitis develops with necrosis of parenchymal pancreatitis tissue (with or without infection) and a Systemic Inflammatory Response Syndrome (SIRS).
In the latter group morbidity and mortality are high. Of these patients 25% will die. Recently, a group of synthetic guanylhydrazone compounds have been developed and one of its representatives CNI-1493 (a p38 Mitogen Activated Protein [MAP] kinase inhibitor) proved to be a very powerful inhibitor of TNF-alpha. In addition, CNI-1493 inhibits a host of other macrophage induced pro-inflammatory cytokines (IL-1, IL-6, MIP-1Ñ and MIP-1Ò).
The primary question that we want to address is whether it is possible with the prophylactic administration of CNI-1493 to lower the incidence of post-ERCP pancreatitis.
Hypothesis:
Prophylactic administration of p38 MAP/c-Jun N-terminal protein Kinase (JNK) inhibitor may decrease the incidence of post-ERCP pancreatitis through inhibition of the pro-inflammatory cytokines IL-1, IL-6, TNF and Macrophage Inflammatory Protein (MIP). In animal studies CNI-1493 or related compounds have been shown to reduce the severity of experimental pancreatitis and pancreatitis associated lung injury.
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Randomised, placebo controlled, parallel group, double blinded trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Endoscopic Retrograde Cholangiopancreatography (ERCP), pancreatitis
Intervention
Single infusion of CNI-1493 (50 mg intravenous [IV] or placebo IV (randomised, double blind) one hour prior to start of ERCP.
Intervention type
Drug
Phase
Not Specified
Drug names
CNI-1493
Primary outcome measure
Does administration of CNI-1493 decrease the incidence of post ERCP pancreatitis in high risk patients undergoing ERCP?
Secondary outcome measures
1. Is CNI-1493 administration safe in patients undergoing ERCP?
2. Does administration of CNI-1493 decrease the severity of post ERCP pancreatitis in high risk patients undergoing ERCP?
3. Does administration of CNI-1493 decrease the incidence of post ERCP hyperamylasemia in high risk patients undergoing ERCP?
4. Does administration of CNI-1493 decrease the levels of post ERCP IL-6, Interleukin-eight (IL-8), TNF and IL-1 in high risk patients undergoing ERCP?
Overall trial start date
01/03/2002
Overall trial end date
31/12/2005
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Included are all patients who do not fit the exclusion criteria and will undergo an ERCP with the intention to:
a. cannulate and visualise the pancreatic duct
b. perform therapeutic procedures (e.g. stenting, balloon dilatation, sphincter manometry, precut papillotomy, stone extraction, (intra-luminal) endosonography, Extracorporeal Shock-Wave Lithotripsy [ESWL] and dilatation) in the pancreatic duct, common bile duct or left and right hepatic ducts
2. Patients must agree to use acceptable means of birth control for at least three months after the procedure
3. Patients must sign informed consent
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
270
Participant exclusion criteria
1. Diagnostic ERCP (low risk)
2. Active pancreatitis at time of ERCP (confounding)
3. Severe abdominal pain pre ERCP (confounding)
4. Age less than 18 years (contra-indication)
5. Known or suspected pregnancy or breast-feeding (contra-indication)
6. ERCP for stent exchange in malignant disease (low risk)
7. Severe chronic pancreatitis (low risk)
8. Kidney failure i.e. serum creatinine greater than 20 mg/dl (greater than 180 µM) (any state, contra-indication)
9. Other anti-TNF therapy (e.g. infliximab) within eight weeks of intended study treatment
Recruitment start date
01/03/2002
Recruitment end date
31/12/2005
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academical Medical Centre
Amsterdam
1105 AZ
Netherlands
Sponsor information
Organisation
Cytokine PharmaSciences, Inc (USA)
Sponsor details
Walnut Hill Plaza
150 South Warner Road
Suite 420
King of Prussia
PA 19406
United States of America
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Cytokine PharmaSciences, Inc (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list