Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Worldwide rates of obesity have doubled in the last 30 years, and obesity has been associated as a risk factor for hospital-acquired infections and increased occurrence of death in critically-ill patients. Piperacillin/tazobactam is a commonly prescribed antibiotic for critically ill patients with an infection, however, limited information exists for dosing this drug in obese patients. In these limited reports, standard doses of piperacillin/tazobactam given to the small number of obese patients resulted in lower blood concentrations, which could lead to inadequate killing of bacteria. The purpose of this study is to compare blood concentrations from standard piperacillin/tazobactam dosing compared to higher dosing regimens in obese patients. This study will also include information on the safety and tolerability of the higher dose regimens. The study investigators believe that the higher dosing regimen will produce adequate blood levels in obese patients and will not add any more risk of harm to obese patients receiving this higher dose.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Dose to High Dose Piperacillin/Tazobactam | Experimental | Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Then, they will be switched to higher dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Piperacillin/Tazobactam Standard Dose to High Dose | Drug | Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Patients will be switched to higher dose after receiving the standard dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Maximum Concentrations for Piperacillin | Pharmacokinetic parameters for piperacillin of maximum serum concentration (Cmax) will be measured in both standard dosing and high dosing. | 0, 1, 3, and 6 hours post-dose |
| Serum Minimum Concentrations of Piperacillin | Minimum serum concentrations (Cmin) of piperacillin will be measured in both standard and high doses | 0, 1, 3, and 6 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Half-life of Piperacillin | Half-life (t1/2) of piperacillin will be calculated from serum concentrations in both standard and high doses | 0, 1, 3, and 6 hours post-dose |
| Volume of Distribution of Piperacillin |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Steven C Forland, PharmD | Loma Linda University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Loma Linda University Medical Center | Loma Linda | California | 92350 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33743171 | Derived | Veillette JJ, Winans SA, Maskiewicz VK, Truong J, Jones RN, Forland SC. Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin-Tazobactam in Obese Patients. Eur J Drug Metab Pharmacokinet. 2021 May;46(3):385-394. doi: 10.1007/s13318-021-00677-1. Epub 2021 Mar 20. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
438 obese patients receiving P-T were screened between June 2013 and January 2016. 67 patients fit inclusion criteria - 12 chose not to participate in the study or informed consent could not be obtained; 9 were excluded due to refusal of the primary care team; 13 had P-T discontinued prior to enrollment; and 4 were included previously in the study
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Piperacillin/Tazobactam Standard to High Dose | Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Then, they will be switched to higher dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Piperacillin/Tazobactam Standard to High Dose | Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Then, they will be switched to higher dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum Maximum Concentrations for Piperacillin | Pharmacokinetic parameters for piperacillin of maximum serum concentration (Cmax) will be measured in both standard dosing and high dosing. | The # of participants in the rows below will be double the overall participant number because each patient had two different dosing regimens of pip/tazo In Group 3, 4.5g group N = 5 represents low and high dose - 2 patients receiving 4.5g upon enrollment and increased to 6.75g; 3 patients were receiving either 2.25g or 3.375g and increased to 4.5g | Posted | Mean | Full Range | milligrams per liter | 0, 1, 3, and 6 hours post-dose |
|
Each patient was monitored daily for adverse reactions from study enrollment until two weeks after piperacillin-tazobactam was discontinued or until hospital discharge, whichever was sooner
Pertinent lab values followed for signs of acute renal impairment, liver impairment, or hematologic abnormalities. Adverse reactions were promptly reported to the primary team and IRB. If study drug suspected to be responsible for an adverse reaction, the drug discontinued at the discretion of the primary care team. There were no deaths out of the 28 subjects at risk of death during study enrollment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Dose to High Dose Piperacillin/Tazobactam | Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Then, they will be switched to higher dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. Piperacillin/Tazobactam Standard Dose to High Dose: Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Patients will be switched to higher dose after receiving the standard dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea and vomiting | Gastrointestinal disorders | Systematic Assessment | Nausea with one episode of vomiting, which resolved upon dose reduction in one patient on the 6.75 grams dose of piperacillin-tazobactam. Naranjo scale gave this a 6 as probably related to study drug. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment | Naranjo scale gave 2 patients a 2 and a 3 respectively, making adverse reaction possibly related to study drug. There were many confounders in these 2 patients regarding reasons for acute kidney injury. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Steven Forland | Loma Linda University Medical Center | 909-558-4000 | 43980 | sforland@llu.edu |
Not provided
| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D010878 | Piperacillin |
| D000078142 | Tazobactam |
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| ID | Term |
|---|---|
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
Volume of distribution (Vd) of piperacillin will be calculated from serum concentrations in both standard and high doses
| 0, 1, 3, and 6 hours post-dose |
| Median |
| Full Range |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). | Median | Full Range | kilograms per sqare meter |
|
| Weight | Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). | Median | Full Range | kilograms |
|
| Total Bilirubin | Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). | Median | Full Range | milligrams per deciliter |
|
| ICU Status | Measure Analysis Population Description: Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). | Count of Participants | Participants |
|
| Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II Score | The APACHE II score is calculated at the beginning of the ICU admission to help determine the patient's mortality risk for the admission The higher the score, the higher the risk of mortality. Approximated Mortality Rate by score 0-4 = 4% 5-9 = 8% 10-14 = 15% 15-19 = 25% 20-24 = 40% 25-29 = 55% 30-34 = 75% >34 = 85% | Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). | Median | Full Range | units on a scale |
|
| Sequential Organ Failure Assessment (SOFA) Score | Scores can be measured on all patients admitted to the intensive care unit in order to determine level of acuity and mortality risk. The higher the score, the higher the mortality risk. Mean SOFA Score Mortality 0-1.0 = 1.2% 1.1-2.0 = 5.4% 2.1-3.0 = 20.0% 3.1-4.0 = 36.1% 4.1-5.0 = 73.1% >5.1 = 84.4% | Measure Analysis Population Description: Patients categorized by degree of renal function. The total number of patients is 28, divided into 4 different groups based on degree of renal insufficiency as measured by creatinine clearance (CrCl). | Median | Full Range | units on a scale |
|
|
|
| Primary | Serum Minimum Concentrations of Piperacillin | Minimum serum concentrations (Cmin) of piperacillin will be measured in both standard and high doses | The # of participants in the rows below will be double the overall participant number because each patient had two different dosing regimens of pip/tazo In Group 3, 4.5g group N = 5 represents low and high dose - 2 patients receiving 4.5g upon enrollment and increased to 6.75g; 3 patients were receiving either 2.25g or 3.375g and increased to 4.5g | Posted | Mean | Full Range | milligrams per liter | 0, 1, 3, and 6 hours post-dose |
|
|
|
| Secondary | Half-life of Piperacillin | Half-life (t1/2) of piperacillin will be calculated from serum concentrations in both standard and high doses | The # of participants in the rows below will be double the overall participant number because each patient had two different dosing regimens of pip/tazo In Group 3, 4.5g group N = 5 represents low and high dose - 2 patients receiving 4.5g upon enrollment and increased to 6.75g; 3 patients were receiving either 2.25g or 3.375g and increased to 4.5g | Posted | Mean | Full Range | hours | 0, 1, 3, and 6 hours post-dose |
|
|
|
| Secondary | Volume of Distribution of Piperacillin | Volume of distribution (Vd) of piperacillin will be calculated from serum concentrations in both standard and high doses | The # of participants in the rows below will be double the overall participant number because each patient had two different dosing regimens of pip/tazo In Group 3, 4.5g group N = 5 represents low and high dose - 2 patients receiving 4.5g upon enrollment and increased to 6.75g; 3 patients were receiving either 2.25g or 3.375g and increased to 4.5g | Posted | Mean | Full Range | liters | 0, 1, 3, and 6 hours post-dose |
|
|
|
| 0 |
| 29 |
| 1 |
| 29 |
| 6 |
| 29 |
|
|
| Nausea | Gastrointestinal disorders | Systematic Assessment | Mild in one patient that resolved while still on high dose of study drug. Naranjo scale gave this a 2 as possibly related to study drug |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment | Patient had cholecystitis and abdominal abscess. Symptoms subsided during treatment course with no dose adjustment. Naranjo scale gave this a 1 for possibly a study drug related event. |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | one episode of loose stool after 4.5 gram dose which resolved spontaneously without dose adjustment. Naranjo scale gave this a 2, possibly related to study drug. |
|
| Delirium | Psychiatric disorders | Systematic Assessment | one patient had acute onset delirium on high dose drug, biting off a few of his fingernails. Patient was also on lorazepam scheduled every 6 hours. Study drug dose reduced and lorazepam discontinued. Patient returned to baseline. Naranjo scale = 3. |
|
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010397 | Penicillanic Acid |
| D013450 | Sulfones |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
|
| Group 1 (CrCl >/= 80 mL/min) on 6.75 grams |
|
|
| Group 1 (CrCl >/= 80 mL/min) on 9 grams |
|
|
| Group 2 (CrCl >/= 40 to 80 mL/min) on 3.375 grams |
|
|
| Group 2 (CrCl >/= 40 to 80 mL/min) on 4.5 grams |
|
|
| Group 2 (CrCl >/= 40 to 80 mL/min) on 6.75 grams |
|
|
| Group 2 (CrCl >/= 40 to 80 mL/min) on 9 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 2.25 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 3.375 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 4.5 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 6.75 grams |
|
|
| Group 4 (HD) on 2.25 grams |
|
|
| Group 4 (HD) on 3.375 grams |
|
|
| Group 4 (HD) on 4.5 grams |
|
|
| Group 4 (HD) on 6.75 grams |
|
|
|
| Group 1 (CrCl >/= 80 mL/min) on 6.75 grams |
|
|
| Group 1 (CrCl >/= 80 mL/min) on 9 grams |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 3.375 gram |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 4.5 grams |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 6.75 grams |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 9 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 2.25 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 3.375 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 4.5 grams |
|
|
| Group 3 (CrCl < 40 mL/min) on 6.75 grams |
|
|
| Group 4 (HD) on 2.25 grams |
|
|
| Group 4 (HD) on 3.375 grams |
|
|
| Group 4 (HD) on 4.5 grams |
|
|
| Group 4 (HD) on 6.75 grams |
|
|
|
| Group 1 (CrCl >/= 80 mL/min) on 6.75 grams |
|
|
| Group 1 (CrCl >/= 80 mL/min) on 9 grams |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 3.375 gram |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 4.5 gram |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 6.75 gram |
|
|
| Group 2 (CrCl >/= 40 to < 80 mL/min) on 9 gram |
|
|
| Group 3 (CrCl < 40mL/min) on 2.25 grams |
|
|
| Group 3 (CrCl < 40mL/min) on 3.375 grams |
|
|
| Group 3 (CrCl < 40mL/min) on 4.5 grams |
|
|
| Group 3 (CrCl < 40mL/min) on 6.75 grams |
|
|
| Group 4 (HD) on 2.25 grams |
|
|
| Group 4 (HD) on 3.375 grams |
|
|
| Group 4 (HD) on 4.5 grams |
|
|
| Group 4 (HD) on 6.75 grams |
|
|