Acute Pancreatitis (AP), Alcoholic Pancreatitis, Cancer Acute Pancreatitis, Gallstone Pancreatitis, Hypertriglyceridemia Acute Pancreatitis, Idiopathic (Unknown) Acute Pancreatitis, Medication Induced Acute Pancreatitis, Miscellaneous (i.e. Acute on Chronic Pancreatitis), Trauma Acute Pancreatitis
Conditions
Keywords
Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis
Brief summary
The purpose of this study was to determine the effects (good and bad) of giving a drug called pentoxifylline to patients with acute pancreatitis.
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.
Interventions
DRUGPentoxifylline
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
DRUGPlacebo
A harmless pill that has no therapeutic effect, used as a control in testing of investigational drug
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-reactive Protein (C-RP) From Admission Baseline at One Week. | Admission (baseline), day 5 | 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 |
| Change in Tumor Necrosis Factor-alpha (TNF-a) Levels From Admission Baseline at One Week. | Admission (baseline), day 5 | 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 |
| Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week. | Admission (baseline), day 5 | 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 |
| Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week. | Admission (baseline), day 5 | 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 |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at Mayo Clinic in Rochester, Minnesota.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Pentoxifylline: Pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which raises intracellular cyclic adenosine monophosphate (cAMP), activates protein kinase A (PKA), inhibits 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 | 45 |
| 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.
Placebo: A harmless pill that has no therapeutic effect, used as a control in testing of investigational drug | 38 |
| Total | 83 |
Baseline characteristics
| Characteristic | Placebo | Pentoxifylline | Total |
|---|---|---|---|
| Age, Continuous | 55.5 years | 63.0 years | 59.0 years |
| Bedside Index of Severity in Acute Pancreatitis (BISAP) Score | 0.5 units on a scale | 1.0 units on a scale | 1.0 units on a scale |
| Race/Ethnicity, Customized Hispanic/Latino | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 36 Participants | 41 Participants | 77 Participants |
| Region of Enrollment United States | 38 Participants | 45 Participants | 83 Participants |
| Sex: Female, Male Female | 21 Participants | 21 Participants | 42 Participants |
| Sex: Female, Male Male | 17 Participants | 24 Participants | 41 Participants |
| Systematic Inflammatory Response Syndrome (SIRS) score on admission | 1.0 units on a scale | 1.0 units on a scale | 1.0 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 45 | 0 / 38 |
| other Total, other adverse events | 12 / 45 | 5 / 38 |
| serious Total, serious adverse events | 1 / 45 | 0 / 38 |
Outcome results
Primary
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
Time frame: Admission (baseline), day 5
Population: Eighteen (18) of forty-five subjects (45) in the treatment arm and eight (8) of thirty-eight (38) subjects in the placebo arm completed the study. Additionally, subjects had blood collections for 5 days or until dismissal. Many subjects were dismissed at 2-3 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pentoxifylline | Change in C-reactive Protein (C-RP) From Admission Baseline at One Week. | Admission (baseline) | 86.2 mg/L | Standard Deviation 81.5 |
| Pentoxifylline | Change in C-reactive Protein (C-RP) From Admission Baseline at One Week. | Day 5 | 116.4 mg/L | Standard Deviation 100.4 |
| Placebo | Change in C-reactive Protein (C-RP) From Admission Baseline at One Week. | Admission (baseline) | 75.8 mg/L | Standard Deviation 83.1 |
| Placebo | Change in C-reactive Protein (C-RP) From Admission Baseline at One Week. | Day 5 | 127.2 mg/L | Standard Deviation 97.8 |
Comparison: Admission (baseline)p-value: 0.5796Kruskal-Wallis
Comparison: Day 5p-value: 0.8415Kruskal-Wallis
Primary
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
Time frame: Admission (baseline), day 5
Population: Eighteen (18) of forty-five subjects (45) in the treatment arm and eight (8) of thirty-eight (38) subjects in the placebo arm completed the study. Additionally, subjects had blood collections for 5 days or until dismissal. Many subjects were dismissed at 2-3 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pentoxifylline | Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week. | Admission (baseline) | 107.9 pg/mL | Standard Deviation 124.8 |
| Pentoxifylline | Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week. | Day 5 | 81.8 pg/mL | Standard Deviation 97.4 |
| Placebo | Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week. | Admission (baseline) | 89.1 pg/mL | Standard Deviation 138.2 |
| Placebo | Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week. | Day 5 | 88.6 pg/mL | Standard Deviation 85.2 |
Comparison: Admission (baseline)p-value: 0.1236Kruskal-Wallis
Comparison: Day 5p-value: 0.9468Kruskal-Wallis
Primary
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
Time frame: Admission (baseline), day 5
Population: Eighteen (18) of forty-five subjects (45) in the treatment arm and eight (8) of thirty-eight (38) subjects in the placebo arm completed the study. Additionally, subjects had blood collections for 5 days or until dismissal. Many subjects were dismissed at 2-3 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pentoxifylline | Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week. | Admission (baseline) | 43.7 pg/ml | Standard Deviation 29.4 |
| Pentoxifylline | Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week. | Day 5 | 45.9 pg/ml | Standard Deviation 43.2 |
| Placebo | Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week. | Admission (baseline) | 31.5 pg/ml | Standard Deviation 26.1 |
| Placebo | Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week. | Day 5 | 32.1 pg/ml | Standard Deviation 23.5 |
Comparison: Admission (baseline)p-value: 0.157Kruskal-Wallis
Comparison: Day 5p-value: 0.3173Kruskal-Wallis
Primary
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
Time frame: Admission (baseline), day 5
Population: Eighteen (18) of forty-five subjects (45) in the treatment arm and eight (8) of thirty-eight (38) subjects in the placebo arm completed the study. Additionally, subjects had blood collections for 5 days or until dismissal. Many subjects were dismissed at 2-3 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pentoxifylline | Change in Tumor Necrosis Factor-alpha (TNF-a) Levels From Admission Baseline at One Week. | Admission (baseline) | 1.9 pg/ml | Standard Deviation 0.9 |
| Pentoxifylline | Change in Tumor Necrosis Factor-alpha (TNF-a) Levels From Admission Baseline at One Week. | Day 5 | 4.3 pg/ml | Standard Deviation 6.3 |
| Placebo | Change in Tumor Necrosis Factor-alpha (TNF-a) Levels From Admission Baseline at One Week. | Admission (baseline) | 1.8 pg/ml | Standard Deviation 1.3 |
| Placebo | Change in Tumor Necrosis Factor-alpha (TNF-a) Levels From Admission Baseline at One Week. | Day 5 | 1.9 pg/ml | Standard Deviation 0.7 |
Comparison: Admission (baseline)p-value: 0.1109Kruskal-Wallis
p-value: 0.4619Kruskal-Wallis