Pentoxifylline Treatment of Acute Pancreatitis

Pentoxifylline Treatment in Acute Pancreatitis; A Double-Blind Placebo-Controlled Randomized Trial

The purpose of this study is to determine the effects (good and bad) of giving a drug called pentoxifylline to patients with acute pancreatitis, to see if it can improve blood tests associated with inflammation (tissue damage). Pentoxifylline is approved by the US Food and Drug Administration (FDA) for treatment of circulation problems, but its use in this study is investigational, which means that the FDA has not approved it for the treatment of pancreatitis. However, the FDA has allowed the use of pentoxifylline in this research study.

Study Overview

• Status: Completed
• Conditions: Acute Pancreatitis
• Intervention / Treatment: Drug: Pentoxifylline; Drug: Placebo

Detailed Description

Subjects will be put in one of two groups by chance (as in the flip of a coin). This is done so that neither you nor the investigator will know which group you are in.

You will be put into either the treatment group or the control group.

• The treatment group will receive a drug called pentoxifylline
• The control group will receive a placebo (matching pill that has no medication in it) You will take the pills by mouth starting from the time of admission. You will receive a total of 9 doses over the first three days of your hospitalization (72 hours).

When subject have standard patient care blood draws, additional blood will be taken to do the research tests. The additional blood tests will be done every day for up to 5 days, after the administration of study drug or till the time of discharge whichever occurs earlier. The additional tests will require about 2 teaspoons (10 ml) of blood per day; the maximum amount of extra blood taken would be less than 3 tablespoons (40.0 ml). Information from your medical record will be gathered while you are hospitalized and after your discharge. The study will continue to gather clinical follow up information up to four months.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Predicted Severe Acute Pancreatitis
2. Enrollment within 72 hours of diagnosis
3. Ability to give informed consent
4. Age >17 years

Exclusion Criteria:

1. Moderate or severe congestive heart failure
2. History of seizure disorder or demyelinating disease
3. Nursing mothers
4. Pregnancy
5. History of prior tuberculosis or risk factors for tuberculosis
6. Evidence of immunosuppression (malignancy, chronic renal failure, chemotherapy within 60 days, ongoing steroid treatment*, and HIV)- (*the exception of prednisone use will be allowed to participate).
7. Evidence of chronic pancreatitis from history and examination (however, "acute on chronic pancreatitis" diagnosis is allowed)
8. Evidence of active or pending hemorrhage.
9. Paralytic ileus with vomiting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pentoxifylline; Pentoxifylline, 400 mg, 3 times daily by mouth from time of enrollment until 72 hours from enrollment. Subjects received up to a maximum of 9 doses.	Drug: Pentoxifylline; 400 mg, 3 times daily by mouth from time of enrollment until 72 hours from enrollment. Subjects received up to a maximum of 9 doses.; Other Names: Trental
Placebo Comparator: Placebo; Placebo, 400 mg, 3 times daily by mouth from time of enrollment until 72 hours from enrollment. Subjects received up to a maximum of 9 doses.	Drug: Placebo; 400 mg, 3 times daily by mouth from time of enrollment until 72 hours from enrollment. Subjects received up to a maximum of 9 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C-Reactive Protein (CRP)	C-reactive protein is produced by the liver. The level of CRP rises when there is inflammation throughout the body. The normal value range for CRP = 1-10 mg/L.	baseline, Day 1, Day 3
Change in Tumor Necrosis Factor (TNF)-Alpha	Normal value range for TNF alpha = 0 - 22 pg/ml.	baseline, Day 1, Day 3
Change in Interleukin (IL) IL-6	Normal value range for IL-6 = 0 - 5 pg/ml.	baseline, Day 1, Day 3
Changes in Interleukin (IL) IL-8	Normal value range for IL-8 = 0 - 5 pg/ml.	baseline, Day 1, Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Of Subjects With New Onset Organ Failure During Hospitalization		1 week or until dismissal date whichever occurs earlier.
Number Of Subjects With New Onset Pancreatic Necrosis During Hospitalization		1 week or until dismissal date whichever occurs earlier
Number of Patients With Lengthy Hospital Stays	"Lengthy" was defined as either greater than 4 days or greater than 10 days.	30 days or until dismissal date, whichever occurs earlier
Length of Hospital Stay		30 days or until dismissal date, whichever occurs earlier
Length of Intensive Care Unit (ICU) Stay		30 days or until dismissal date, whichever occurs earlier
Number of Subjects Who Needed an Intensive Care Unit Stay		30 days, or until dismissal, whichever came first

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Santhi S Vege, MD, Mayo Clinic

Publications and helpful links

General Publications

• Vege SS, Atwal T, Bi Y, Chari ST, Clemens MA, Enders FT. Pentoxifylline Treatment in Severe Acute Pancreatitis: A Pilot, Double-Blind, Placebo-Controlled, Randomized Trial. Gastroenterology. 2015 Aug;149(2):318-20.e3. doi: 10.1053/j.gastro.2015.04.019. Epub 2015 Jun 23.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 19, 2010
• First Submitted That Met QC Criteria: February 8, 2011
• First Posted (Estimate): February 9, 2011

Study Record Updates

• Last Update Posted (Estimate): October 25, 2016
• Last Update Submitted That Met QC Criteria: September 14, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: pancreatitis; pancreatic necrosis; severe acute pancreatitis (SAP); Alcoholic pancreatitis; gallstone pancreatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: 08-006648