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| ID | Type | Description | Link |
|---|---|---|---|
| DORICPK4003 | Other Identifier | other |
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| Name | Class |
|---|---|
| Ortho-McNeil Janssen Scientific Affairs, LLC | INDUSTRY |
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The study hypothesis is to measure how the drug doripenem is cleared from the body of critically ill trauma patients. The investigators will measure blood drug concentrations and calculate how much the drug distributes in the body and how fast it is removed from the body. There is little information on how drugs are cleared in critically ill patients and the wrong dose of a drug could make it ineffective. The investigators will use this information to predict the most reasonable dose to treat infections effectively in these patients.
Understanding the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of an antibiotic can provide insight into developing appropriate dosing regimens. It is even more imperative at the present time to maximize PK/PD parameters since there are no new novel antimicrobial agents to treat resistant gram-negative infections. This approach allows us to achieve superior PD parameters and treat bacteria that would have been resistant to standard dosing due to higher minimum inhibitory concentrations (MICs).
Doripenem exhibits time-dependent bactericidal activity and the pharmacodynamic parameter predicting clinical and bacteriologic outcomes is the percentage of the dosing interval that free drug concentrations remain above the minimum inhibitory concentration (T > MIC) of the infecting pathogen Sepsis is known to influence drug pharmacokinetics and pharmacodynamics as a result of changes in hemodynamics, capillary permeability, third spacing, acid-base status, serum proteins, and organ function. Moreover, trauma patients tend to be younger with fewer comorbidities. They are hypermetabolic and are often given aggressive fluid resuscitation resulting in increased renal clearance of drugs and a larger volume of distribution. As a consequence of these differences in PK parameters, the calculated PD parameters will likely differ resulting in sub-optimal T> MIC. For time-dependent antibacterial agents such as doripenem, the T > MIC is one of the most important pharmacodynamic parameters in predicting clinical efficacy, therefore it is imperative to evaluate the PK parameters in this particular population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doripenem group | Experimental | Patients will receive doripenem for the treatment of their infection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doripenem | Drug | Doripenem 1 gm administered over 4 hours X 3 doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Volume of Distribution (Vd) | The Volume of distribution is the calculated volume that the given amount of drug is uniformly distributed in the body to achieve a particular concentration | After 3rd dose of study medication |
| Clearance (CL) | Clearance is the volume of drug removed from the body per unit of time (hrs). | After 3rd dose of study medication |
| Elimination Constant (ke) | The elimination rate constant of a drug from the central compartment | after 3rd dose of study drug |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Salomone, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grady Memorial Hospital | Atlanta | Georgia | 30303 | United States |
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Patients recruited from April 2010 to July 2011. All patients were admitted to the Surgical ICU during the study period
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| ID | Title | Description |
|---|---|---|
| FG000 | Doripenem Group | Patients will receive doripenem 1 gm IV over 4 hours X 3 doses for the empiric treatment of an infection |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Doripenem Group | Patients will receive doripenem 1 gm IV over 4 hours X 3 doses for the empiric treatment of an infection |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Volume of Distribution (Vd) | The Volume of distribution is the calculated volume that the given amount of drug is uniformly distributed in the body to achieve a particular concentration | Patients that completed the study and did not have atypical variations in the measurement of serum concentrations were included in the final evaluation | Posted | Mean | Standard Deviation | liters | After 3rd dose of study medication |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Doripenem Group | Patients will receive doripenem 1 gm IV over 4 hours X 3 doses for the empiric treatment of an infection |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lower gastrointestinal | Gastrointestinal disorders | Systematic Assessment | Not related to drug |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prasad Abraham | Grady Health System | 404-616-3246 | pabraham@gmh.edu |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D014947 | Wounds and Injuries |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000077726 | Doripenem |
| ID | Term |
|---|---|
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 |
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
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| Participants |
|
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| Primary | Clearance (CL) | Clearance is the volume of drug removed from the body per unit of time (hrs). | Patients that completed the study and did not have atypical variations in the measurement of serum concentrations were included in the final evaluation | Posted | Mean | Standard Deviation | liters per hour | After 3rd dose of study medication |
|
|
|
| Primary | Elimination Constant (ke) | The elimination rate constant of a drug from the central compartment | Patients that completed the study and did not have atypical variations in the measurement of serum concentrations were included in the final evaluation | Posted | Mean | Standard Deviation | per hour | after 3rd dose of study drug |
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| 8 |
| 30 |
| 0 |
| 30 |
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| cardiac arrest | Cardiac disorders | Systematic Assessment | Not related to drug |
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| Post operative wound | Skin and subcutaneous tissue disorders | Systematic Assessment | post operative wound infection. Not related to drug |
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| atrial fibrillation | Cardiac disorders | Systematic Assessment | Not related to drug |
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| deep vein thrombosis | Vascular disorders | Systematic Assessment | Doubtful if related to drug |
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| renal failure acute | Renal and urinary disorders | Systematic Assessment | Not related to drug |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |