Does mitogen activated protein kinase inhibition with CNI-1493 prevent post-Endoscopic retrograde cholangiopancreatography pancreatitis?
| ISRCTN | ISRCTN26235881 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN26235881 |
| Protocol serial number | N/A |
| Sponsor | Cytokine PharmaSciences, Inc (USA) |
| Funder | Cytokine PharmaSciences, Inc (USA) |
- Submission date
- 20/12/2005
- Registration date
- 20/12/2005
- Last edited
- 20/08/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr M J Bruno
Scientific
Scientific
Academical Medical Centre
Department of Gastroenterology-Hepatology (MDL)
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
| m.j.bruno@amc.uva.nl |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised, placebo controlled, parallel group, double blinded trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | Does mitogen activated protein kinase inhibition with CNI-1493 prevent post-Endoscopic retrograde cholangiopancreatography pancreatitis? |
| Study acronym | CNI study |
| Study objectives | 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(s) | Ethics approval received from the local medical ethics committee |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | CNI-1493 |
| Primary outcome measure(s) |
Does administration of CNI-1493 decrease the incidence of post ERCP pancreatitis in high risk patients undergoing ERCP? |
| Key secondary outcome measure(s) |
1. Is CNI-1493 administration safe in patients undergoing ERCP? |
| Completion date | 31/12/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Not Specified |
| Target sample size at registration | 270 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/03/2002 |
| Date of final enrolment | 31/12/2005 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Academical Medical Centre
Amsterdam
1105 AZ
Netherlands
1105 AZ
Netherlands
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
20/08/2021: Proactive update review. No publications found. Search options exhausted.
