Acute Pancreatitis
Conditions
Keywords
pancreatitis, pancreatic necrosis, severe acute pancreatitis (SAP), Alcoholic pancreatitis, gallstone pancreatitis
Brief summary
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.
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.
Interventions
DRUGPentoxifylline
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.
DRUGPlacebo
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.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-Reactive Protein (CRP) | baseline, Day 1, Day 3 | 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. |
| Change in Tumor Necrosis Factor (TNF)-Alpha | baseline, Day 1, Day 3 | Normal value range for TNF alpha = 0 - 22 pg/ml. |
| Change in Interleukin (IL) IL-6 | baseline, Day 1, Day 3 | Normal value range for IL-6 = 0 - 5 pg/ml. |
| Changes in Interleukin (IL) IL-8 | baseline, Day 1, Day 3 | Normal value range for IL-8 = 0 - 5 pg/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Intensive Care Unit (ICU) Stay | 30 days or until dismissal date, whichever occurs earlier | — |
| Number Of Subjects With New Onset Organ Failure During Hospitalization | 1 week 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 | — |
| 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 | 30 days or until dismissal date, whichever occurs earlier | Lengthy was defined as either greater than 4 days or greater than 10 days. |
| Length of Hospital Stay | 30 days or until dismissal date, whichever occurs earlier | — |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from the Mayo Clinic in Rochester, Minnesota between 2009 and 2012.
Pre-assignment details
30 subjects signed informed consent; two subjects were excluded after consent because they were found to be not eligible.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 14 |
| 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. | 14 |
| Total | 28 |
Baseline characteristics
| Characteristic | Pentoxifylline | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69 years | 58 years | 64 years |
| Body Mass Index | 30.2 kg/m^2 | 32.5 kg/m^2 | 30.3 kg/m^2 |
| Region of Enrollment United States | 14 participants | 14 participants | 28 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
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.
Time frame: baseline, Day 1, Day 3
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pentoxifylline | Change in C-Reactive Protein (CRP) | Change from baseline to Day 1 | 48.4 mg/L |
| Pentoxifylline | Change in C-Reactive Protein (CRP) | Change from baseline to Day 3 | 62 mg/L |
| Placebo | Change in C-Reactive Protein (CRP) | Change from baseline to Day 1 | 60.6 mg/L |
| Placebo | Change in C-Reactive Protein (CRP) | Change from baseline to Day 3 | 154 mg/L |
Comparison: Change from Day 0 to Day 1. p\<0.05 was considered statistically significant.p-value: 0.62Wilcoxon (Mann-Whitney)
Comparison: Change from Day 0 to Day 3. p\<0.05 was considered statistically significant.p-value: 1Wilcoxon (Mann-Whitney)
Primary
Change in Interleukin (IL) IL-6
Normal value range for IL-6 = 0 - 5 pg/ml.
Time frame: baseline, Day 1, Day 3
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pentoxifylline | Change in Interleukin (IL) IL-6 | Change from baseline to Day 1 | 2.1 pg/ml |
| Pentoxifylline | Change in Interleukin (IL) IL-6 | Change from baseline to Day 2 | -8.6 pg/ml |
| Placebo | Change in Interleukin (IL) IL-6 | Change from baseline to Day 1 | 0.7 pg/ml |
| Placebo | Change in Interleukin (IL) IL-6 | Change from baseline to Day 2 | -2.9 pg/ml |
Comparison: Change from Day 0 to Day 1. p\<0.05 was considered statistically significant.p-value: 0.58Wilcoxon (Mann-Whitney)
Comparison: Change from Day 0 to Day 3. p\<0.05 was considered statistically significant.p-value: 0.8Wilcoxon (Mann-Whitney)
Primary
Change in Tumor Necrosis Factor (TNF)-Alpha
Normal value range for TNF alpha = 0 - 22 pg/ml.
Time frame: baseline, Day 1, Day 3
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pentoxifylline | Change in Tumor Necrosis Factor (TNF)-Alpha | Change from baseline to Day 1 | 0 pg/ml |
| Pentoxifylline | Change in Tumor Necrosis Factor (TNF)-Alpha | Change from baseline to Day 3 | 0.2 pg/ml |
| Placebo | Change in Tumor Necrosis Factor (TNF)-Alpha | Change from baseline to Day 1 | -0.05 pg/ml |
| Placebo | Change in Tumor Necrosis Factor (TNF)-Alpha | Change from baseline to Day 3 | -0.3 pg/ml |
Comparison: Change from Day 0 to Day 1. p\<0.05 was considered statistically significant.p-value: 0.72Wilcoxon (Mann-Whitney)
Comparison: Change from Day 0 to Day 3. p\<0.05 was considered statistically significant.p-value: 0.5Wilcoxon (Mann-Whitney)
Primary
Changes in Interleukin (IL) IL-8
Normal value range for IL-8 = 0 - 5 pg/ml.
Time frame: baseline, Day 1, Day 3
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pentoxifylline | Changes in Interleukin (IL) IL-8 | Change from baseline to Day 1 | -3.0 pg/ml |
| Pentoxifylline | Changes in Interleukin (IL) IL-8 | Change from baseline to Day 3 | 0.35 pg/ml |
| Placebo | Changes in Interleukin (IL) IL-8 | Change from baseline to Day 1 | -1.7 pg/ml |
| Placebo | Changes in Interleukin (IL) IL-8 | Change from baseline to Day 3 | -1.9 pg/ml |
Comparison: Change from Day 0 to Day 1. p\<0.05 was considered statistically significant.p-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Change from Day 0 to Day 3. p\<0.05 was considered statistically significant.p-value: 0.56Wilcoxon (Mann-Whitney)
Secondary
Length of Hospital Stay
Time frame: 30 days or until dismissal date, whichever occurs earlier
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pentoxifylline | Length of Hospital Stay | 3 days |
| Placebo | Length of Hospital Stay | 5 days |
Comparison: P \< 0.05 was considered statistically significant.p-value: 0.06t-test, 2 sided
Secondary
Length of Intensive Care Unit (ICU) Stay
Time frame: 30 days or until dismissal date, whichever occurs earlier
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pentoxifylline | Length of Intensive Care Unit (ICU) Stay | 0 Days |
| Placebo | Length of Intensive Care Unit (ICU) Stay | 0 Days |
Comparison: P \< 0.05 was considered statistically significant.p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
Number of Patients With Lengthy Hospital Stays
Lengthy was defined as either greater than 4 days or greater than 10 days.
Time frame: 30 days or until dismissal date, whichever occurs earlier
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pentoxifylline | Number of Patients With Lengthy Hospital Stays | Length of hospitalization >4 days | 2 participants |
| Pentoxifylline | Number of Patients With Lengthy Hospital Stays | Length of hospitalization >10 days | 0 participants |
| Placebo | Number of Patients With Lengthy Hospital Stays | Length of hospitalization >4 days | 8 participants |
| Placebo | Number of Patients With Lengthy Hospital Stays | Length of hospitalization >10 days | 5 participants |
Comparison: Comparison between arms for length of hospitalization \> 4 days. P \< 0.05 was considered statistically significant.p-value: 0.04t-test, 2 sided
Comparison: Comparison was for length of hospitalization \>10 days. P \< 0.05 was considered statistically significant.p-value: 0.03t-test, 2 sided
Secondary
Number of Subjects Who Needed an Intensive Care Unit Stay
Time frame: 30 days, or until dismissal, whichever came first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pentoxifylline | Number of Subjects Who Needed an Intensive Care Unit Stay | 0 participants |
| Placebo | Number of Subjects Who Needed an Intensive Care Unit Stay | 4 participants |
Comparison: P \< 0.05 was considered statistically significant.p-value: 0.04Wilcoxon (Mann-Whitney)
Secondary
Number Of Subjects With New Onset Organ Failure During Hospitalization
Time frame: 1 week or until dismissal date whichever occurs earlier.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pentoxifylline | Number Of Subjects With New Onset Organ Failure During Hospitalization | 0 participants |
| Placebo | Number Of Subjects With New Onset Organ Failure During Hospitalization | 3 participants |
Comparison: p\<0.05 was considered statistically significant.p-value: 0.09Wilcoxon (Mann-Whitney)
Secondary
Number Of Subjects With New Onset Pancreatic Necrosis During Hospitalization
Time frame: 1 week or until dismissal date whichever occurs earlier
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pentoxifylline | Number Of Subjects With New Onset Pancreatic Necrosis During Hospitalization | 0 participants |
| Placebo | Number Of Subjects With New Onset Pancreatic Necrosis During Hospitalization | 2 participants |
Comparison: p\<0.05 was considered statistically significant.p-value: 0.22Wilcoxon (Mann-Whitney)