Ventilator Associated PneumoniaIMPACTNCT00950222
Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic
A study testing Imipenem/Amikacin in people with Ventilator Associated Pneumonia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The study is a prospective open trial conducted in 4 centers, and designed to determine if pharmacokinetic (PK) and pharmacodynamic (PD) parameters of imipenem, associated with amikacin as empirical therapy, impact microbiological and clinical outcome of patients with Gram negative bacilli (GNB) ventilator-associated… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator Associated Pneumonia
- What is being tested?
- Imipenem/Amikacin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2009to Jan 2012
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Mechanical ventilation for more than 48 hours
- Clinical suspicion of VAP defined by a new persistent radiological infiltrate and one of the following signs: purulent tracheal aspirations, or temperature of 38°3 or higher, or leucocyte count > 10000/ml
- Risk of multi resistant bacteria defined as follows: at least 6 days of mechanical ventilation or antibiotic treatment in the 15 previous days
- Distal pulmonary secretion sample obtained beforehand for microbiological diagnosis by bronchoalveolar lavage via bronchoscopy or blinded protected telescoping catheter via bronchoscopy or blindly
- Presence of GNB on direct examination of the distal pulmonary secretion sample
- Realization of a preliminary medical examination. 8- Written inform consent from the patient or relatives. The consent may be obtained after the enrollment if the patient is not able to give consent and if there is no relatives
Who cannot join
- Time between distal pulmonary secretion sample taking and the 1st administration of imipenem exceeding 24 hours
- Pregnancy
- Severely impaired renal function (creatinine clearance lower than 10 mL/mn or renal replacement therapy)
- Allergy to imipenem or amikacin
- Treatment in progress with imipenem or amikacin
- Death expected within 48 hours following diagnosis of VAP
Show all 9Show fewer
- Myasthenia
- Simultaneous administration of others aminoglycosides
- Association with intravenous polymyxin or botulinum toxin
Trial locations and contacts
1 site in 1 country.
About this study
The study is a prospective open trial conducted in 4 centers, and designed to determine if pharmacokinetic (PK) and pharmacodynamic (PD) parameters of imipenem, associated with amikacin as empirical therapy, impact microbiological and clinical outcome of patients with Gram negative bacilli (GNB) ventilator-associated pneumonia (VAP).
Read the detailed description
Inappropriate initial antibiotherapy increases mortality of many serious infections. This is the case for ventilator-associated pneumonia, frequently occurring during intensive care unit (ICU) hospitalization, and whose 48 first hours of treatment are decisive.
It is well established that pharmacokinetic and pharmacodynamic parameters of antibiotics are correlated with their clinical and microbiological effectiveness. However in ICU patients, pharmacokinetic parameters of antibiotics suffer great variations, and bacteria responsible for these infections are usually less sensitive to antibiotics, especially Gram negative bacilli (GNB). An important pharmacodynamic variability may occur at the initial phase of the antibiotic treatment, decisive for the infection's outcome.
We propose to evaluate the correlation between pharmacokinetic and pharmacodynamic profile of the empirical antibiotic therapy and the microbiological and clinical outcome of VAP.
- Conditions
- Ventilator Associated Pneumonia
- Being tested
- Imipenem/Amikacin
- Keywords
- Intensive care unit, Ventilator associated pneumonia, Gram negative bacilli infection, Empirical antibiotic therapy, Pharmacokinetic / pharmacodynamic, Imipenem, Amikacin, Gram negative bacilli
- Medical subject headings
- Pneumonia, Ventilator-Associated, Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imipenem/AmikacinDrug
Also called Therapy for VAP imipenem associated with amikacin
patients will received as empirical therapy for VAP imipenem associated with amikacin.
| Study group | Role | What they receive |
|---|---|---|
| 1:Imipenem/Amikacin | Experimental | patients will receive as empirical therapy for VAP imipenem associated with amikacin.After primary outcome measure, antibiotic therapy will be left at the discretion of the physician in charge of the patient.
Imipenem: recommended usual dosage for VAP treatment, IV (in the vein), every 8 hours
Amikacin: recommended usual dosage for VAP treatment (20mg/kg), IV (in the vein), single dose (at H0) for the 48 first hours of treatment Receives: Drug: Imipenem/Amikacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variation of numeration (cfu per ml) of GNB, for whom culture of pulmonary samples are positive (higher than defined thresholds), between the quantitative endotracheal aspiration (QAE) obtained at H0 (initiation of treatment) and QAE obtained at H48
Measured: Hour 48
Secondary outcomes (12)
To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP
Measured: Hour 24
To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP
Measured: Hour 24
To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved
Measured: Hour 24
To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP
Measured: Hour 24
To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3
Measured: Day 3
To assess the impact of imipenem and amikacin PK/PD parameters variability on the CPIS, clinical score of VAP, measured 48 hours after initiation of the treatment
Measured: Hour 48
To assess the impact of imipenem and amikacin PK/PD parameters on the time necessary to observe a CPIS lower or equal to 6
Measured: Day 8
To assess the impact of imipenem and amikacin PK/PD parameters on clinical evolution of the VAP after 7 days of antibiotic treatment
Measured: Day 8
To assess the impact of imipenem and amikacin PK/PD parameters on serum procalcitonin levels evolution between the initiation of the treatment and 48 hours after the initiation of the treatment of the VAP
Measured: Hour 48
To assess the impact of imipenem and amikacin PK/PD parameters on mortality at day 28 (Day 28) 11- to assess the impact of imipenem and amikacin PK/PD parameters on VAP relapse
Measured: Day 28
To study emergence of less sensitive bacteria to imipenem and/or amikacin, 48 hours after the initiation of the antibiotic treatment, among GNB isolated in endotracheal aspiration before initiation of this treatment
Measured: Hour 48
To study emergence in the tracheal and digestive flora of micro-organisms resistant to imipenem after the first 48 hours of treatment by imipenem
Measured: Hour 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2009 (estimated)
- Study startJun 2009
- Primary completionSep 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ventilator Associated PneumoniaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier PAJOT, MD, Principal investigator, HOPITAL ARGENTEUIL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00950222
- Sponsor's protocol ID
- P061014
- Other IDs
- CRC06049
- Acronym
- IMPACT
- Status last verified
- Jul 2012
- First submitted
- 28 Jul 2009
- Last updated
- 26 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Burdet C, Pajot O, Couffignal C, Armand-Lefevre L, Foucrier A, Laouenan C, Wolff M, Massias L, Mentre F. Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. Eur J Clin Pharmacol. 2015 Jan;71(1):75-83. doi: 10.1007/s00228-014-1766-y. Epub 2014 Oct 21.
PubMed 25327505Couffignal C, Pajot O, Laouenan C, Burdet C, Foucrier A, Wolff M, Armand-Lefevre L, Mentre F, Massias L. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens. Br J Clin Pharmacol. 2014 Nov;78(5):1022-34. doi: 10.1111/bcp.12435.
PubMed 24903189
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic
- ClinicalTrials.gov ID
- NCT00950222
- Acronym / sponsor ID
- IMPACT / P061014
- Conditions
- Ventilator Associated Pneumonia
- Keywords
- Intensive care unit, Ventilator associated pneumonia, Gram negative bacilli infection, Empirical antibiotic therapy, Pharmacokinetic / pharmacodynamic, Imipenem, Amikacin, Gram negative bacilli
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 31 Jul 2009 (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.
The study is a prospective open trial conducted in 4 centers, and designed to determine if pharmacokinetic (PK) and pharmacodynamic (PD) parameters of imipenem, associated with amikacin as empirical therapy, impact microbiological and clinical outcome of patients with Gram negative bacilli (GNB) ventilator-associated pneumonia (VAP).
Detailed description
Inappropriate initial antibiotherapy increases mortality of many serious infections. This is the case for ventilator-associated pneumonia, frequently occurring during intensive care unit (ICU) hospitalization, and whose 48 first hours of treatment are decisive.
It is well established that pharmacokinetic and pharmacodynamic parameters of antibiotics are correlated with their clinical and microbiological effectiveness. However in ICU patients, pharmacokinetic parameters of antibiotics suffer great variations, and bacteria responsible for these infections are usually less sensitive to antibiotics, especially Gram negative bacilli (GNB). An important pharmacodynamic variability may occur at the initial phase of the antibiotic treatment, decisive for the infection's outcome.
We propose to evaluate the correlation between pharmacokinetic and pharmacodynamic profile of the empirical antibiotic therapy and the microbiological and clinical outcome of VAP.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1:Imipenem/Amikacin | Experimental | Drug: Imipenem/Amikacinpatients will receive as empirical therapy for VAP imipenem associated with amikacin.After primary outcome measure, antibiotic therapy will be left at the discretion of the physician in charge of the patient. Imipenem: recommended usual dosage for VAP treatment, IV (in the vein), every 8 hours Amikacin: recommended usual dosage for VAP treatment (20mg/kg), IV (in the vein), single dose (at H0) for the 48 first hours of treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 years
- Mechanical ventilation for more than 48 hours
- Clinical suspicion of VAP defined by a new persistent radiological infiltrate and one of the following signs: purulent tracheal aspirations, or temperature of 38°3 or higher, or leucocyte count > 10000/ml
- Risk of multi resistant bacteria defined as follows: at least 6 days of mechanical ventilation or antibiotic treatment in the 15 previous days
- Distal pulmonary secretion sample obtained beforehand for microbiological diagnosis by bronchoalveolar lavage via bronchoscopy or blinded protected telescoping catheter via bronchoscopy or blindly
Key exclusion criteria (9 listed)
- Time between distal pulmonary secretion sample taking and the 1st administration of imipenem exceeding 24 hours
- Pregnancy
- Severely impaired renal function (creatinine clearance lower than 10 mL/mn or renal replacement therapy)
- Allergy to imipenem or amikacin
- Treatment in progress with imipenem or amikacin
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 |
|---|---|---|
| Imipenem/AmikacinAlso: Therapy for VAP imipenem associated with amikacinpatients will received as empirical therapy for VAP imipenem associated with amikacin. | Drug | 1:Imipenem/Amikacin |
Primary outcome
Variation of numeration (cfu per ml) of GNB, for whom culture of pulmonary samples are positive (higher than defined thresholds), between the quantitative endotracheal aspiration (QAE) obtained at H0 (initiation of treatment) and QAE obtained at H48
Time frame: Hour 48
12 secondary outcomes
To describe imipenem and amikacin PK parameters as empirical therapy in ICU patients treated for VAP
Time frame: Hour 24
To describe imipenem and amikacin PD parameters as empirical therapy in ICU patients treated for VAP
Time frame: Hour 24
To determine the proportion of patients for whom the pharmacodynamic targets suggested in the literature for aminoglycosides and beta lactams are achieved
Time frame: Hour 24
To identify sources of variability of imipenem and amikacin PK/PD parameters in ICU patients with VAP
Time frame: Hour 24
To assess the impact of imipenem and amikacin PK/PD parameters on GNB eradication at day 3
Time frame: Day 3
To assess the impact of imipenem and amikacin PK/PD parameters variability on the CPIS, clinical score of VAP, measured 48 hours after initiation of the treatment
Time frame: Hour 48
To assess the impact of imipenem and amikacin PK/PD parameters on the time necessary to observe a CPIS lower or equal to 6
Time frame: Day 8
To assess the impact of imipenem and amikacin PK/PD parameters on clinical evolution of the VAP after 7 days of antibiotic treatment
Time frame: Day 8
To assess the impact of imipenem and amikacin PK/PD parameters on serum procalcitonin levels evolution between the initiation of the treatment and 48 hours after the initiation of the treatment of the VAP
Time frame: Hour 48
To assess the impact of imipenem and amikacin PK/PD parameters on mortality at day 28 (Day 28) 11- to assess the impact of imipenem and amikacin PK/PD parameters on VAP relapse
Time frame: Day 28
To study emergence of less sensitive bacteria to imipenem and/or amikacin, 48 hours after the initiation of the antibiotic treatment, among GNB isolated in endotracheal aspiration before initiation of this treatment
Time frame: Hour 48
To study emergence in the tracheal and digestive flora of micro-organisms resistant to imipenem after the first 48 hours of treatment by imipenem
Time frame: Hour 48
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 26 Jul 2012.
- Derived from this study: PubMed 25327505Burdet C, Pajot O, Couffignal C, Armand-Lefevre L, Foucrier A, Laouenan C, Wolff M, Massias L, Mentre F. Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. Eur J Clin Pharmacol. 2015 Jan;71(1):75-83. doi: 10.1007/s00228-014-1766-y. Epub 2014 Oct 21.
- Derived from this study: PubMed 24903189Couffignal C, Pajot O, Laouenan C, Burdet C, Foucrier A, Wolff M, Armand-Lefevre L, Mentre F, Massias L. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens. Br J Clin Pharmacol. 2014 Nov;78(5):1022-34. doi: 10.1111/bcp.12435.
Related trials for Ventilator Associated Pneumonia
Not yet recruitingObservational study
Traditional Chinese Medicine in Multidrug-Resistant Bacterial Pneumonia
Multi Drug Resistant Infections, Pneumnia
Not yet recruitingObservational study
Early Identification of Pathogens in Children With Respiratory Tract Infection by Mechanical Ventilation Using mNGS
VAP - Ventilator Associated Pneumonia
RecruitingPhase 4
EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics
Blood Stream Infections, Ventilator Associated Pneumonia
Not yet recruiting
Mobile-Based Microlearning for Improving ICU Nurses' Adherence to Ventilator-Associated Pneumonia Prevention Protocols
Ventilator-Associated Pneumonia
Not yet recruitingPhase 3
Cefepime-Zidebactam Versus Ceftazidime-Avibactam With or Without Colistin for Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia
Hospital Acquired Bacterial Pneumonia (HABP), Ventilator Associated Bacterial Pneumonia (VABP)
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.
Olivier PAJOT, MD principal investigator
HOPITAL ARGENTEUIL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Imipenem/Amikacin in people with Ventilator Associated Pneumonia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 7 inclusion and 9 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 26 Jul 2012. 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 France. 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.
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?
Variation of numeration (cfu per ml) of GNB, for whom culture of pulmonary samples are positive (higher than defined thresholds), between the quantitative endotracheal aspiration (QAE) obtained at H0 (initiation of treatment) and QAE obtained at H48 (time frame: Hour 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00950222, which also lists 2 linked publications.
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 26 Jul 2012.