Condition category
Digestive System
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
05/03/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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-1ƒÑ and MIP-1ƒÒ).

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 measures

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

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

http://www.cytokinepharmasciences.com/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes