SepsisPhase 4NCT01027897
Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients
A Phase 4 study testing Doripenem in people with Sepsis, run by Emory University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Sepsis
- What is being tested?
- Doripenem
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Dec 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients With Sepsis at Grady Health System
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.
Read the 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.
- Conditions
- Sepsis
- Being tested
- Doripenem
- Keywords
- Pharmacokinetics, Pharmacodynamics, Doripenem, Trauma, sepsis, Trauma patients with sepsis
- Medical subject headings
- Sepsis, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoripenemDrug
Doripenem 1 gm administered over 4 hours X 3 doses
| Study group | Role | What they receive |
|---|---|---|
| Doripenem group | Experimental | Patients will receive doripenem for the treatment of their infection Receives: Drug: Doripenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: After 3rd dose of study medication
Clearance (CL)
Clearance is the volume of drug removed from the body per unit of time (hrs).
Measured: After 3rd dose of study medication
Elimination Constant (ke)
The elimination rate constant of a drug from the central compartment
Measured: after 3rd dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
- Study startApr 2010
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Ortho-McNeil Janssen Scientific Affairs, LLC
- Responsible party
- Sponsor
- Investigators
- Jeffrey Salomone, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01027897
- Sponsor's protocol ID
- IRB00016181a
- Other IDs
- DORICPK4003
- Status last verified
- Dec 2013
- First submitted
- 8 Dec 2009
- Last updated
- 27 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients With Sepsis at Grady Health System
- ClinicalTrials.gov ID
- NCT01027897
- Acronym / sponsor ID
- IRB00016181a
- Conditions
- Sepsis
- Keywords
- Pharmacokinetics, Pharmacodynamics, Doripenem, Trauma, sepsis, Trauma patients with sepsis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Ortho-McNeil Janssen Scientific Affairs, LLC
- Study start
- Apr 2010
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 9 Dec 2009 (estimated)
- Results
- Posted 25 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doripenem group | Experimental | Drug: DoripenemPatients will receive doripenem for the treatment of their infection |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoripenemDoripenem 1 gm administered over 4 hours X 3 doses | Drug | Doripenem group |
Primary outcome
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
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).
Elimination Constant (ke)
Time frame: after 3rd dose of study drug
The elimination rate constant of a drug from the central compartment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Salomone, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doripenem in people with Sepsis, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume of Distribution (Vd) (time frame: After 3rd dose of study medication). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2014.