Ventilator-Associated PneumoniaPhase 4NCT01467648
The Pharmacodynamics of Doripenem Between 4-hour and 1-hour Infusion in Patients With Ventilator-associated Pneumonia
A Phase 4 study testing Doripenem in people with Ventilator-Associated Pneumonia, run by Sutep Jaruratanasirikul at 1 site in Thailand.
Trial summary
This is prospective and randomized study to assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Ventilator-Associated Pneumonia
- What is being tested?
- Doripenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteThailand
- Study dates
- Oct 2010to Oct 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged ≥ 20 years
- Patients who have VAP with Gram negative bacilli infections. The diagnosis of VAP was defined by a new and persistent infiltrate on chest radiography associated with at least one of the following: purulent tracheal secretions; temperature of 38.3°C or higher; a leukocyte count higher than 10,000/mm3
Who cannot join
- Patients who have documented hypersensitivity to doripenem or other carbapenems.
- Patients who have an estimated creatinine clearance of ≤ 50 ml/min
- Patients who are in circulatory shock (defined as a systolic blood pressure of < 90 mmHg).
- Patients who are pregnant.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Prince of Songkla University
Hat Yai, Changwat Songkhla, 90110
About this study
This is prospective and randomized study to assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion.
Clinical and laboratory data such as Age,Sex, Body weight, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Blood culture will be collected.
Read more
Twelve patients will be enrolled in this study. After completion of the doripenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.
Doripenem pharmacokinetic study will be carried out during the doripenem therapy. Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.
Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.
The doripenem assays by method of Ikeda K et al. (J Chromatogr B, 2008) will be performed.
Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)
Read the detailed description
Introduction:
The treatment of resistant pathogens is becoming more difficult, and only a few novel antimicrobial agents are currently in development with activity against highly resistant Gram negative bacteria. Doripenem is a carbapenem antibacterial agent with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. This agent is often used as the last line of therapy for highly resistant Gram negative bacilli nosocomial pathogens. In common with other beta-lactam, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with the therapeutic efficacy is the time that concentrations in the tissue and serum are above the MIC (t>MIC). However, in tropical countries the stability of carbapenem antibiotics is an important consideration when considering continuous infusion. Therefore, prolonged infusion may be a useful route of administration to maximize bactericidal activity. In addition, pharmacokinetic changes have been found for several antimicrobial agents in critically ill patients, including ventilator-associated pneumonia. However, until now we have had no data to reveal the PK/PD index of doripenem in these critically ill patients.
Objectives:
To assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion.
Clinical and laboratory data: Age,Sex, Body weight, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Blood culture
Drug preparation and administration:
Doripenem will be reconstituted with saline solution according to the manufacturer's guidelines and then administered to the patients by 2 regimens:
1.0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 4 h every 8 h.
2.0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h.
Study design:
The study is planned as a prospective and randomized in patients with VAP. Each patients will receive doripenem in 2 regimens at room temperature (37°C) consecutively: (i) infusion of 0.5 g of doripenem for 4 h via an infusion pump at a constant flow rate every 8 h; (ii) infusion of 0.5 g of doripenem for 1 h via an infusion pump at a constant flow rate every 8 h.
Twelve patients will be enrolled in this study. After completion of the doripenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.
Sample collections:
Doripenem pharmacokinetic study will be carried out during the doripenem therapy.
Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.
Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.
All blood samples will be allowed to clot and then cebtrifuged at 2,000g.
The serum obtained will be stored at-80°C until analysis.
Doripenem assay:
The doripenem assays by method of Ikeda K et al. (J Chromatogr B, 2008) will be performed at Department of Medicine, Faculty of Medicine.
Clinical data and pathogens collection:
- Initial patient demographic data (age, sex, weight, diagnosis, APACHE II scores) will be collected upon enrollment in the study.
- The Gram negative bacilli isolated from sputum in 12 patients will be collected and the MIC of the doripenem for pathogens will be determined by E tests upon enrollment in the study.
Duration of study:
Patients will receive doripenem for 3 days
Pharmacokinetic and pharmacodynamic analysis:
Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)
Sample Size: Twelve patients with VAP will be enrolled in this study.
- Conditions
- Ventilator-Associated Pneumonia
- Being tested
- Doripenem
- Keywords
- Infection, Doripenem, Ventilator-Associated Pneumonia, pharmacokinetic, pharmacodynamic
- Medical subject headings
- Pneumonia, Ventilator-Associated, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoripenemDrug
Also called Doripenem (Doribax)
(i) 0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h.
Blood samples (approximately 2 ml)will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.
DoripenemDrug
Also called Doripenem (Doribax)
(ii) 0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h.
Blood samples (approximately 2 ml) will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.
| Study group | Role | What they receive |
|---|---|---|
| 0.5 g by 4 hour infusion | Experimental | Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem. Receives: Drug: Doripenem |
| 0.5 g by 1 hour infusion | Experimental | Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem. Receives: Drug: Doripenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of doripenem in plasma
Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response).
Measured: 8 hours profile after 7th dose of doripenem
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2011 (estimated)
- Study startOct 2010
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ventilator-Associated PneumoniaStudies of the same condition, open and under way.
- 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sutep Jaruratanasirikul
- Sponsor type
- University, hospital or other
- Collaborators
- Prince of Songkla University
- Responsible party
- Sponsor-investigator, Sutep Jaruratanasirikul, Prince of Songkla University
- Investigators
- Sutep Jaruratanasirikul, MD, Principal investigator, Prince of Songkha
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01467648
- Sponsor's protocol ID
- DORINOS4004
- Status last verified
- Nov 2011
- First submitted
- 31 Oct 2011
- Last updated
- 9 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pharmacodynamics of Doripenem Between 4-hour and 1-hour Infusion in Patients With Ventilator-associated Pneumonia
- ClinicalTrials.gov ID
- NCT01467648
- Acronym / sponsor ID
- DORINOS4004
- Conditions
- Ventilator-Associated Pneumonia
- Keywords
- Infection, Doripenem, Ventilator-Associated Pneumonia, pharmacokinetic, pharmacodynamic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Sutep JaruratanasirikulUniversity, hospital or other
- Collaborators
- Prince of Songkla University
- Study start
- Oct 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 9 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is prospective and randomized study to assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion.
Clinical and laboratory data such as Age,Sex, Body weight, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Blood culture will be collected.
Twelve patients will be enrolled in this study. After completion of the doripenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.
Doripenem pharmacokinetic study will be carried out during the doripenem therapy. Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.
Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.
The doripenem assays by method of Ikeda K et al. (J Chromatogr B, 2008) will be performed.
Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)
Detailed description
Introduction:
The treatment of resistant pathogens is becoming more difficult, and only a few novel antimicrobial agents are currently in development with activity against highly resistant Gram negative bacteria. Doripenem is a carbapenem antibacterial agent with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. This agent is often used as the last line of therapy for highly resistant Gram negative bacilli nosocomial pathogens. In common with other beta-lactam, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with the therapeutic efficacy is the time that concentrations in the tissue and serum are above the MIC (t>MIC). However, in tropical countries the stability of carbapenem antibiotics is an important consideration when considering continuous infusion. Therefore, prolonged infusion may be a useful route of administration to maximize bactericidal activity. In addition, pharmacokinetic changes have been found for several antimicrobial agents in critically ill patients, including ventilator-associated pneumonia. However, until now we have had no data to reveal the PK/PD index of doripenem in these critically ill patients.
Objectives:
To assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion.
Clinical and laboratory data: Age,Sex, Body weight, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Blood culture
Drug preparation and administration:
Doripenem will be reconstituted with saline solution according to the manufacturer's guidelines and then administered to the patients by 2 regimens:
1.0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 4 h every 8 h.
2.0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h.
Study design:
The study is planned as a prospective and randomized in patients with VAP. Each patients will receive doripenem in 2 regimens at room temperature (37°C) consecutively: (i) infusion of 0.5 g of doripenem for 4 h via an infusion pump at a constant flow rate every 8 h; (ii) infusion of 0.5 g of doripenem for 1 h via an infusion pump at a constant flow rate every 8 h.
Twelve patients will be enrolled in this study. After completion of the doripenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.
Sample collections:
Doripenem pharmacokinetic study will be carried out during the doripenem therapy.
Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.
Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.
All blood samples will be allowed to clot and then cebtrifuged at 2,000g.
The serum obtained will be stored at-80°C until analysis.
Doripenem assay:
The doripenem assays by method of Ikeda K et al. (J Chromatogr B, 2008) will be performed at Department of Medicine, Faculty of Medicine.
Clinical data and pathogens collection:
- Initial patient demographic data (age, sex, weight, diagnosis, APACHE II scores) will be collected upon enrollment in the study.
- The Gram negative bacilli isolated from sputum in 12 patients will be collected and the MIC of the doripenem for pathogens will be determined by E tests upon enrollment in the study.
Duration of study:
Patients will receive doripenem for 3 days
Pharmacokinetic and pharmacodynamic analysis:
Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)
Sample Size: Twelve patients with VAP will be enrolled in this study.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 0.5 g by 4 hour infusion | Experimental | Drug: DoripenemBlood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem. |
| 0.5 g by 1 hour infusion | Experimental | Drug: DoripenemBlood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients aged ≥ 20 years
- Patients who have VAP with Gram negative bacilli infections. The diagnosis of VAP was defined by a new and persistent infiltrate on chest radiography associated with at least one of the following: purulent tracheal secretions; temperature of 38.3°C or higher; a leukocyte count higher than 10,000/mm3
Key exclusion criteria (4 listed)
- Patients who have documented hypersensitivity to doripenem or other carbapenems.
- Patients who have an estimated creatinine clearance of ≤ 50 ml/min
- Patients who are in circulatory shock (defined as a systolic blood pressure of < 90 mmHg).
- Patients who are pregnant.
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 |
|---|---|---|
| DoripenemAlso: Doripenem (Doribax)(i) 0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h. Blood samples (approximately 2 ml)will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem. | Drug | 0.5 g by 4 hour infusion |
| DoripenemAlso: Doripenem (Doribax)(ii) 0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h. Blood samples (approximately 2 ml) will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem. | Drug | 0.5 g by 1 hour infusion |
Primary outcome
Concentration of doripenem in plasma
Time frame: 8 hours profile after 7th dose of doripenem
Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2011.
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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.
Sutep Jaruratanasirikul, MD principal investigator
Prince of Songkha
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 Ventilator-Associated Pneumonia, run by Sutep Jaruratanasirikul at 1 site in Thailand.
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 2 inclusion and 4 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 9 Nov 2011. 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 Thailand. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Concentration of doripenem in plasma (time frame: 8 hours profile after 7th dose of doripenem). 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 9 Nov 2011.