Trial Outcomes & Findings for Pentoxifylline Treatment in Acute Pancreatitis (AP) (NCT NCT02487225)
NCT ID: NCT02487225
Last Updated: 2019-01-23
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
83 participants
Primary outcome timeframe
Admission (baseline), day 5
Results posted on
2019-01-23
Participant Flow
Subjects were recruited at Mayo Clinic in Rochester, Minnesota.
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
45
|
38
|
|
Overall Study
COMPLETED
|
18
|
8
|
|
Overall Study
NOT COMPLETED
|
27
|
30
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pentoxifylline Treatment in Acute Pancreatitis (AP)
Baseline characteristics by cohort
| Measure |
Pentoxifylline
n=45 Participants
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
|
Placebo
n=38 Participants
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
|
Total
n=83 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Age, Continuous
|
63.0 years
n=5 Participants
|
55.5 years
n=7 Participants
|
59.0 years
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
41 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
45 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Bedside Index of Severity in Acute Pancreatitis (BISAP) Score
|
1.0 units on a scale
n=5 Participants
|
0.5 units on a scale
n=7 Participants
|
1.0 units on a scale
n=5 Participants
|
|
Systematic Inflammatory Response Syndrome (SIRS) score on admission
|
1.0 units on a scale
n=5 Participants
|
1.0 units on a scale
n=7 Participants
|
1.0 units on a scale
n=5 Participants
|
PRIMARY outcome
Timeframe: Admission (baseline), day 5Population: 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.
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
Outcome measures
| Measure |
Pentoxifylline
n=45 Participants
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
|
Placebo
n=38 Participants
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
|
|---|---|---|
|
Change in C-reactive Protein (C-RP) From Admission Baseline at One Week.
Admission (baseline)
|
86.2 mg/L
Standard Deviation 81.5
|
75.8 mg/L
Standard Deviation 83.1
|
|
Change in C-reactive Protein (C-RP) From Admission Baseline at One Week.
Day 5
|
116.4 mg/L
Standard Deviation 100.4
|
127.2 mg/L
Standard Deviation 97.8
|
PRIMARY outcome
Timeframe: Admission (baseline), day 5Population: 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.
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
Outcome measures
| Measure |
Pentoxifylline
n=40 Participants
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
|
Placebo
n=37 Participants
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
|
|---|---|---|
|
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
|
1.8 pg/ml
Standard Deviation 1.3
|
|
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
|
1.9 pg/ml
Standard Deviation 0.7
|
PRIMARY outcome
Timeframe: Admission (baseline), day 5Population: 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.
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
Outcome measures
| Measure |
Pentoxifylline
n=42 Participants
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
|
Placebo
n=35 Participants
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
|
|---|---|---|
|
Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week.
Admission (baseline)
|
107.9 pg/mL
Standard Deviation 124.8
|
89.1 pg/mL
Standard Deviation 138.2
|
|
Change in Interleukin-6 (IL-6) Levels From Admission Baseline at One Week.
Day 5
|
81.8 pg/mL
Standard Deviation 97.4
|
88.6 pg/mL
Standard Deviation 85.2
|
PRIMARY outcome
Timeframe: Admission (baseline), day 5Population: 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.
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
Outcome measures
| Measure |
Pentoxifylline
n=42 Participants
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
|
Placebo
n=36 Participants
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
|
|---|---|---|
|
Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week.
Admission (baseline)
|
43.7 pg/ml
Standard Deviation 29.4
|
31.5 pg/ml
Standard Deviation 26.1
|
|
Change in Interleukin-8 (IL-8) Levels From Admission Baseline at One Week.
Day 5
|
45.9 pg/ml
Standard Deviation 43.2
|
32.1 pg/ml
Standard Deviation 23.5
|
Adverse Events
Pentoxifylline
Serious events: 1 serious events
Other events: 12 other events
Deaths: 2 deaths
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pentoxifylline
n=45 participants at risk
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
|
Placebo
n=38 participants at risk
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
|
|---|---|---|
|
Psychiatric disorders
Hospitalized for psychological evaluation, considered a danger to self
|
2.2%
1/45 • Number of events 1 • 4 months
|
0.00%
0/38 • 4 months
|
Other adverse events
| Measure |
Pentoxifylline
n=45 participants at risk
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
|
Placebo
n=38 participants at risk
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
|
|---|---|---|
|
General disorders
Sepsis due to disease progression
|
4.4%
2/45 • Number of events 2 • 4 months
|
0.00%
0/38 • 4 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/45 • 4 months
|
2.6%
1/38 • Number of events 1 • 4 months
|
|
General disorders
Headache/Migraine
|
2.2%
1/45 • Number of events 1 • 4 months
|
5.3%
2/38 • Number of events 2 • 4 months
|
|
Cardiac disorders
Angina
|
4.4%
2/45 • Number of events 2 • 4 months
|
0.00%
0/38 • 4 months
|
|
Gastrointestinal disorders
Necrosis due to disease progression
|
2.2%
1/45 • Number of events 1 • 4 months
|
2.6%
1/38 • Number of events 1 • 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.2%
1/45 • Number of events 1 • 4 months
|
0.00%
0/38 • 4 months
|
|
Gastrointestinal disorders
Infected cystic duct leak
|
2.2%
1/45 • Number of events 1 • 4 months
|
0.00%
0/38 • 4 months
|
|
Musculoskeletal and connective tissue disorders
Hip pain and gait dysfunction
|
2.2%
1/45 • Number of events 1 • 4 months
|
0.00%
0/38 • 4 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
2.2%
1/45 • Number of events 1 • 4 months
|
0.00%
0/38 • 4 months
|
|
Gastrointestinal disorders
Nausea
|
4.4%
2/45 • Number of events 2 • 4 months
|
2.6%
1/38 • Number of events 1 • 4 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place