Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Sepsis |
Drug: Doripenem |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients With Sepsis at Grady Health System |
- Volume of Distribution (Vd) [ Time Frame: After 3rd dose of study medication ] [ Designated as safety issue: No ]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
- Clearance (CL) [ Time Frame: After 3rd dose of study medication ] [ Designated as safety issue: No ]Clearance is the volume of drug removed from the body per unit of time (hrs).
- Elimination Constant (ke) [ Time Frame: after 3rd dose of study drug ] [ Designated as safety issue: No ]The elimination rate constant of a drug from the central compartment
| Enrollment: | 30 |
| Study Start Date: | April 2010 |
| Study Completion Date: | December 2011 |
| Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Doripenem group
Patients will receive doripenem for the treatment of their infection
|
Drug: Doripenem
Doripenem 1 gm administered over 4 hours X 3 doses
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years to 90 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients are 18 years of age or older
- Admitted to Emory surgical intensive care unit (ICU) service
- Have a diagnosis of sepsis that requires empiric antimicrobial therapy
- Obtained written informed consent from the patient or a first-degree relative if the patient is unable to give informed consent due to his/her medical condition prior to initiation of any study procedure
Exclusion Criteria:
- Surgical ICU length of stay less than 24 hours
- Acute or chronic renal dysfunction (urine output less than 0.5 mL/kg/hr or calculated creatinine clearance of less than 50 mL/min)
- Pregnancy
- Known allergy to beta-lactam antibiotics
- Non-English-speaking patients
Contacts and Locations| United States, Georgia | |
| Grady Memorial Hospital | |
| Atlanta, Georgia, United States, 30303 | |
| Principal Investigator: | Jeffrey Salomone, MD | Emory University |
More Information
No publications provided
| Responsible Party: | Jeffrey P. Salomone, MD, Associate professor, Emory University |
| ClinicalTrials.gov Identifier: | NCT01027897 History of Changes |
| Other Study ID Numbers: | DORICPK4003 |
| Study First Received: | December 8, 2009 |
| Results First Received: | April 5, 2012 |
| Last Updated: | August 25, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Emory University:
|
Pharmacokinetics Pharmacodynamics Doripenem |
Trauma sepsis Trauma patients with sepsis |
Additional relevant MeSH terms:
|
Critical Illness Sepsis Toxemia Disease Attributes |
Pathologic Processes Infection Systemic Inflammatory Response Syndrome Inflammation |
ClinicalTrials.gov processed this record on May 23, 2013