Clinical trial NCT02641561
Conditions: Post-ERCP Acute Pancreatitis
Keywords: Pancreatitis ERCP Indomethacin Lactated ringer's
Sponsor: The Cooper Health System
Start date: 2014-10-01; Completion date: 2016-06-01
Enrollment: 192 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Post-ERCP pancreatitis is a well-known and sometimes life-threatening complication of ERCP. Both LR and rectal indomethacin have shown benefit in preventing post-ERCP pancreatitis. Despite this, no study to date has evaluated both of these measures for preventing post-ERCP pancreatitis. It is our hope to evaluate the combination of these two modalities for preventing post-ERCP pancreatitis compared with either modality alone.

Detailed description:
Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used diagnostic and therapeutic intervention used in Gastroenterology. At Cooper University Hospital (CUH), we perform approximately 700 ERCPs per year. A known complication of ERCP is post-ERCP pancreatitis. The incidence of post-ERCP pancreatitis has been cited at anywhere from 2.6-3.5% of cases. Also, severe acute pancreatitis has been cited at rates of 0.32-0.4% and death 0.11%.

Recent literature has cited the use of several modalities useful in preventing post-ERCP pancreatitis. Among the modalities evaluated non-steroidal anti-inflammatory drugs (NSAIDS), specifically rectal indomethacin, have demonstrated benefit in preventing post-ERCP. In particular Elmunzer et al demonstrated a benefit in those with sphincter of oddi dysfunction (SOD) and those deemed "high risk" for post-ERCP pancreatitis. Other medication such at octreotoide and corticosteroid have shown mixed results.

Additionally, recent studies have demonstrated the use of lactated ringer's solution (LR) in lieu of normal saline (NS) in patient's with acute pancreatitis. Due to this thought process a recent study evaluated the use of LR in preventing post-ERCP pancreatitis. The results of this study showed that no patients who received aggressive LR hydration developed post-ERCP pancreatitis.

As rectal indomethacin and LR infusion appear to have the most definitive evidence for preventing post-ERCP pancreatitis, it is our hope to evaluate the combination of these two therapies for the prevention of post-ERCP pancreatitis.

This is a double blinded, randomized prospective cohort study involving 4 treatment groups undergoing ERCP.

All treatment arms shall receive consent, pre-procedural risk stratification, demographic data and pre-procedural liker pain scale. All subjects shall receive a study subject number and undergo randomization. All subjects also will receive post-procedural likert pain scale assessment, day 1 and 30 questioning. Treatment arms shall be separated into whether subjects are high risk or not defined in.

Time 0 (Visit 1):

Subjects undergo standard pre-procedural evaluation by nursing, anesthesia and consent for procedure/anesthesia.

The subject shall then be evaluated for study participation and subsequently consented if they desire to be part of the study. They may also undergo informed consent prior to the day of their procedure during their normal office visit. All subjects must have Liver function tests (LFTs), amylase and lipase levels drawn prior to their ERCP test. Subjects will be excluded from study participation if they have acute pancreatitis defined as;

The diagnosis of AP is most often established by the presence of 2 of the 3 following criteria:

(i) abdominal pain consistent with the disease (ii) serum amylase and / or lipase greater than three times the upper limit of normal, and / or (iii) characteristic findings from abdominal imaging

The day of their procedure, nursing shall then obtain intravenous peripheral access (standard for ERCP). Initial demographic data and risk factor data shall be obtained. Subjects shall then be randomized to one of the four study arms and given a study number randomly generated:

Pending which treatment arm the patient is enrolled into the subject shall then receive the above listed therapies and undergo their procedure.

Post-procedure the interventions performed during the ERCP shall be recorded and the patient will go through the standard recovery process. Post-procedure after recovery from anesthesia, the patients shall then be evaluated for the presence of pain after ERCP testing on the standard likert pain scale.

If the subject's pain has substantially increased from baseline, subjects shall then be admitted to the hospital and LFTs, a lipase and amylase level shall be drawn and abdominal imaging ordered if needed by the admitting physician (all the standard of care).

Time 1 Days (Visit 2 via phone):

Subjects shall be called 24 hours from ERCP to assess;

1. Presence/absence of pain
2. If pain, the severity
3. Performance of amylase and lipase
4. Whether admission, urgent care or emergency department visit did occur

Time 1-30 Days The investigator will await the subjects laboratory values and if \> 3 times the upper limit of normal contact the subject via phone.

Time 30 Days (Visit 3 via phone):

Subjects shall be contacted via phone 30 days from ERCP to assess;

1. Presence/absence of pain
2. If pain, the severity
3. Whether admission, urgent care or Emergency Department (ED) visit did occur to a healthcare facility
4. Study summary

To detect a difference of 0.24 vs 0.05 a minimum of 48 per group would be needed (using p=0.05).

Descriptive statistics will be used to summarize demographic variables such as age, gender, race, length of stay, as well diagnosis and disease characteristics such as reasons for ERCP, disease intervention, pain,and outcome variables. Data tables will be generated for those variables with means, standard deviation (SD), medians, interquartile range (IQR), and confidence interval (CI). The Chi-Square test will be used to determine the main effect of treatment on ERCP induced pancreatitis. Nonparametric tests will be used to analyze categorical data while normally distributed data will be analyzed using ANOVA to look for treatment effect on other variables of interest.

Binary and Multinomial Logistic Regression will be used to examine predictors of outcome within treatments and across treatments by building interactions into the model (e.g. reasons for ERCP, intervention type). Data analysis will be performed using Systat version 13 and SPSS version 22. A p\<0.05 will be considered statistically significant.

Arms: arm 1: Normal Saline (intravenous during procedure) + Placebo (100mg suppository per rectum prior to procedure ) arm 2: Normal Saline (intravenous during procedure) + Indomethacin (100mg suppository per rectum prior to procedure ) arm 3: Lactated ringer's solution (1 Liter, intravenous prior to procedure) + Placebo (100mg suppository per rectum prior to procedure) arm 4: Lactated ringer's solution (1 Liter, intravenous prior to procedure) + Indomethacin (100mg suppository per rectum prior to procedure)
Interventions: intervention 1: Indomethacin intervention 2: Lactated Ringer's Solution intervention 3: Normal Saline intervention 4: Placebo
Intervention descriptions: intervention 1: Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) which is commonly used to reduce inflammation caused by gout, osteoarthritis and rheumatoid arthritis. It acts by blocking the cyclo-oxygenase 1 and 2 (COX) receptors. It has also been implicated to prevent post-ERCP pancreatitis intervention 2: Lactated ringer's solution (LR), is an intravenous fluid (IVF) used commonly during endoscopic procedures and operative procedures. It's composition is similar to that of humans including sodium, chloride, potassium, calcium and lactate. Studies have implicated the use of this fluid in pancreatitis treatment and prevention of post-ERCP pancreatitis intervention 3: standard IVF would include 0.9% normal saline (NS) solution used during all endoscopic procedures. 0.9% NS includes equal parts sodium and chloride. intervention 4: Placebo would be a suppository 50 mg x 2

Protocol documents: