Pentoxifylline Treatment in Acute Pancreatitis (AP) (AP)

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

The purpose of this study was to determine the effects (good and bad) of giving a drug called pentoxifylline to patients with acute pancreatitis.

Study Overview

• Status: Completed
• Conditions: Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)
• Intervention / Treatment: Drug: Pentoxifylline; Drug: Placebo

Detailed Description

Participants were randomized to either the treatment group (Pentoxifylline medication) or the control group (Placebo).

Participant took a pill orally, starting from the time of admission. Participants received a total of 9 doses over the three days of hospitalization (72 hours).

Research blood draws were done at baseline and on 5 successive days or until the time of discharge, whichever occured earlier. The study gathered clinical follow up information up to 4 months following hospitalization regarding the diagnosis of acute pancreatitis.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Enrollment within 72 hours of diagnosis of acute pancreatitis (AP)
• Ability to give informed consent or a Legal Adult Representative (LAR) able to give informed consent for subject when needed as defined buy LAR use guidelines.
• Adult subjects of age ≥18 years.

Exclusion Criteria:

• Moderate or severe congestive heart failure
• History of seizure disorders or demyelinating disease
• Nursing mothers
• Pregnancy
• History of prior tuberculosis or risk factors for tuberculosis
• Evidence of non- corticosteroid immunosuppression (such as malignancy, chronic renal failure, chemotherapy within 60 days, and HIV)
• Evidence of active hemorrhage
• Paralytic ileus with severe nausea and vomiting

Study Plan

How is the study designed?

Design Details

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

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 to receive up to a maximum of 9 doses.	Drug: Pentoxifylline; Pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cyclic adenosine monophosphate (cAMP), activates protein kinase A (PKA), inhibits Tumor Necrosis Factor (TNF) and leukotriene synthesis, and reduces inflammation and innate immunity. In addition, pentoxifylline improves red blood cell deformability (known as a haemorrheologic effect), reduces blood viscosity and decreases the potential for platelet aggregation and thrombus formation.Pentoxifylline is also an antagonist at adenosine 2 receptors; Other Names: Trental; Pentoxil; Pentox; Flexital
Placebo Comparator: Placebo; Placebo 3 times daily by mouth from time of enrollment until 72 hours from enrollment. Subjects to receive up to a maximum of 9 doses.	Drug: Placebo; A harmless pill that has no therapeutic effect, used as a control in testing of investigational drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C-reactive Protein (C-RP) From Admission Baseline at One Week.	C-reactive protein is a substance produced by the liver in response to inflammation. Normal C-RP levels are below 3.0 mg/L.Units: mg/L	Admission (baseline), day 5
Change in Tumor Necrosis Factor-alpha (TNF-a) Levels From Admission Baseline at One Week.	Tumor Necrosis Factor Alpha is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. TNF is important to the body because it helps regulate the response of the immune system to a foreign object, especially to the present cancerous tumor. It promotes inflammation, produces other cells used in the inflammatory response, and can help cells heal. The normal range is 5 to 27.2 pg/ml.Units: pg/ml	Admission (baseline), day 5
Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week.	Interleukin-6 (IL-6) may be used to help evaluate a person who has a condition associated with inflammation, such as lupus or rheumatoid arthritis, or with infection, such as sepsis. It may also be used in the evaluation of diabetes or cardiovascular disease. IL-6 is a cytokine, a protein produced by immune cells that acts on other cells to help regulate and/or promote an immune response. It also stimulates the production of acute phase reactants, proteins that increase in the blood with conditions that cause inflammation or tissue injury. Circulating IL-6 can be found in the blood of normal individuals in the 1 pg/mL range, with slight elevations during the menstrual cycle, modest elevations in certain cancers (melanoma) (10 pg/mL), and large elevations after surgery (30-430 pg/mL).Units: pg/ml	Admission (baseline), day 5
Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week.	IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. Units: pg/mL	Admission (baseline), day 5

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Santhi Swaroop Vege, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): April 30, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: June 29, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Metabolic Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Pathological Conditions, Anatomical; Lipid Metabolism Disorders; Gallbladder Diseases; Biliary Tract Diseases; Hyperlipidemias; Dyslipidemias; Pancreatic Diseases; Calculi; Cholelithiasis; Cholecystolithiasis; Alcohol-Induced Disorders; Pancreatitis; Hypertriglyceridemia; Pancreatitis, Chronic; Gallstones; Pancreatitis, Alcoholic; 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: 15-001710; 1R21DK101889-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No