Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients

Sepsis Clinical Trial

Official title:

Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients With Sepsis at Grady Health System

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01027897
• Other study ID #: IRB00016181a
• Secondary ID: DORICPK4003
• Status: Completed
• Phase: Phase 4
• First received: December 8, 2009
• Last updated: December 19, 2013
• Start date: April 2010
• Est. completion date: December 2011

Study information

• Verified date: December 2013
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Sepsis

Intervention

Drug:
• Doripenem
Doripenem 1 gm administered over 4 hours X 3 doses

Locations

Country	Name	City	State
United States	Grady Memorial Hospital	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Ortho-McNeil Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	After 3rd dose of study medication	No
Primary	Clearance (CL)	Clearance is the volume of drug removed from the body per unit of time (hrs).	After 3rd dose of study medication	No
Primary	Elimination Constant (ke)	The elimination rate constant of a drug from the central compartment	after 3rd dose of study drug	No