Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients

This study has been completed.
Sponsor:
Collaborator:
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Emory University
ClinicalTrials.gov Identifier:
NCT01027897
First received: December 8, 2009
Last updated: December 19, 2013
Last verified: December 2013
  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

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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
Criteria

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01027897

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

No publications provided

Responsible Party: Emory University
ClinicalTrials.gov Identifier: NCT01027897     History of Changes
Other Study ID Numbers: IRB00016181a, DORICPK4003
Study First Received: December 8, 2009
Results First Received: April 5, 2012
Last Updated: December 19, 2013
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 September 11, 2014