Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01027897
Recruitment Status : Completed
First Posted : December 9, 2009
Results First Posted : September 25, 2012
Last Update Posted : January 27, 2014
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Emory University

Brief Summary:
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 or disease Intervention/treatment Phase
Sepsis Drug: Doripenem Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients With Sepsis at Grady Health System
Study Start Date : April 2010
Primary Completion Date : December 2011
Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Doripenem
U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Volume of Distribution (Vd) [ Time Frame: After 3rd dose of study medication ]
    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

  2. Clearance (CL) [ Time Frame: After 3rd dose of study medication ]
    Clearance is the volume of drug removed from the body per unit of time (hrs).

  3. Elimination Constant (ke) [ Time Frame: after 3rd dose of study drug ]
    The elimination rate constant of a drug from the central compartment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01027897

United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
Ortho-McNeil Janssen Scientific Affairs, LLC
Principal Investigator: Jeffrey Salomone, MD Emory University

Responsible Party: Emory University Identifier: NCT01027897     History of Changes
Other Study ID Numbers: IRB00016181a
DORICPK4003 ( Other Identifier: other )
First Posted: December 9, 2009    Key Record Dates
Results First Posted: September 25, 2012
Last Update Posted: January 27, 2014
Last Verified: December 2013

Keywords provided by Emory University:
Trauma patients with sepsis

Additional relevant MeSH terms:
Critical Illness
Systemic Inflammatory Response Syndrome
Pathologic Processes
Disease Attributes