Septic ShockPhase 3PAACSNCT02820987
PK/PD of Extended-infusion Meropenem, Piperacillin-tazobactam and Cefepime in the Early Phase of Septic Shock
A Phase 3 study testing MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME in people with Septic Shock, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial summary
This study evaluates PK/PD of an extended-infusion protocol of meropenem, piperacillin-tazobactam and cefepime, in the early phase of septic shock. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 1 siteFrance
- Study dates
- 27 Sep 2016to 4 Oct 2018
- Phase
- Phase 3
- 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
- Septic shock
- Meropenem, piperacillin-tazobactam or cefepime started after enrollment
Who cannot join
- Pregnancy
- Central nervous system infection
- Burns
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics and Pharmacodynamic (PK/PD) of Extended-infusion Meropenem, Piperacillin-tazobactam and Cefepime in the Early Phase of Septic Shock
This study evaluates PK/PD of an extended-infusion protocol of meropenem, piperacillin-tazobactam and cefepime, in the early phase of septic shock.
Read the detailed description
Beta Lactams are the keystones of shock septic treatment. Early phase of septic shock is a period of disturbed pharmacokinetics, with augmented renal clearance and distribution volume of hydrophilic drugs as Beta Lactams. Consequently, early phase of septic shock is a period at risk of underdosing Beta Lactam, which could increase the risk of clinical failure an mortality.
Data are available concerning underdosing of MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME, when administered in bolus.
No data exist concerning the achievement of a target of 100% of the whole interval above 4 time the superior breakpoint of Pseudomonas Aeruginosa according to EUCAST (European Committee on Antimicrobial Susceptibility Testing), during the 48 first hours of treatment of septic shock, when Beta Lactam are administered in extended infusion.
- Conditions
- Septic Shock
- Being tested
- MEROPENEM, PIPERACILLIN-TAZOBACTAM, CEFEPIME
- Keywords
- Septic shock, Beta Lactams, Extended infusion, PK/PD
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEROPENEMDrug
Administration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion.
PIPERACILLIN-TAZOBACTAMDrug
Administration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion.
CEFEPIMEDrug
Administration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion.
| Study group | Role | What they receive |
|---|---|---|
| MEROPENEM | Active comparator | After enrollment, patients of MEROPENEM arm will receive an initial 2g bolus of MEROPENEM and 2g infusion over 3 hours every eight hours, during 48 hours, without modification of rhythm and dose according to renal function. Receives: Drug: MEROPENEM |
| PIPERACILLIN-TAZOBACTAM | Active comparator | After enrollment, patients of PIPERACILLIN - TAZOBACTAM arm will receive an initial 4g bolus of PIPERACILLIN - TAZOBACTAM and a 16g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. Receives: Drug: PIPERACILLIN-TAZOBACTAM |
| CEFEPIME | Active comparator | After enrollment, patients of CEFEPIME arm will receive an initial 2g bolus of CEFEPIME and a 6g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. Receives: Drug: CEFEPIME |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients achieving the PK/PD target
Proportion of patients achieving the target of 100% of 48 first hours of treatment above 4 time the upper critical breakpoint for Pseudomonas Aeruginosa
Measured: First 48 hours
Secondary outcomes (1)
All cause mortality
Measured: 28th day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2016 (estimated)
- Study start27 Sep 2016
- Primary completion4 Oct 2018
- Study completion4 Oct 2018
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 Septic ShockStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02820987
- Sponsor's protocol ID
- 15/493
- Acronym
- PAACS
- Status last verified
- Jul 2018
- First submitted
- 29 Jun 2016
- Last updated
- 16 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. doi: 10.1186/cc9091. Epub 2010 Jul 1.
PubMed 20594297Winiszewski H, Despres C, Puyraveau M, Lagoutte-Renosi J, Montange D, Besch G, Floury SP, Chaignat C, Labro G, Vettoretti L, Clairet AL, Capellier G, Vivet B, Piton G. beta-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study. J Crit Care. 2022 Feb;67:141-146. doi: 10.1016/j.jcrc.2021.10.023. Epub 2021 Nov 9.
PubMed 34768176
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamic (PK/PD) of Extended-infusion Meropenem, Piperacillin-tazobactam and Cefepime in the Early Phase of Septic Shock
- ClinicalTrials.gov ID
- NCT02820987
- Acronym / sponsor ID
- PAACS / 15/493
- Conditions
- Septic Shock
- Keywords
- Septic shock, Beta Lactams, Extended infusion, PK/PD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Study start
- 27 Sep 2016 (actual)
- Primary completion
- 4 Oct 2018 (actual)
- Study completion
- 4 Oct 2018 (actual)
- First posted
- 1 Jul 2016 (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 study evaluates PK/PD of an extended-infusion protocol of meropenem, piperacillin-tazobactam and cefepime, in the early phase of septic shock.
Detailed description
Beta Lactams are the keystones of shock septic treatment. Early phase of septic shock is a period of disturbed pharmacokinetics, with augmented renal clearance and distribution volume of hydrophilic drugs as Beta Lactams. Consequently, early phase of septic shock is a period at risk of underdosing Beta Lactam, which could increase the risk of clinical failure an mortality.
Data are available concerning underdosing of MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME, when administered in bolus.
No data exist concerning the achievement of a target of 100% of the whole interval above 4 time the superior breakpoint of Pseudomonas Aeruginosa according to EUCAST (European Committee on Antimicrobial Susceptibility Testing), during the 48 first hours of treatment of septic shock, when Beta Lactam are administered in extended infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MEROPENEM | Active comparator | Drug: MEROPENEMAfter enrollment, patients of MEROPENEM arm will receive an initial 2g bolus of MEROPENEM and 2g infusion over 3 hours every eight hours, during 48 hours, without modification of rhythm and dose according to renal function. |
| PIPERACILLIN-TAZOBACTAM | Active comparator | Drug: PIPERACILLIN-TAZOBACTAMAfter enrollment, patients of PIPERACILLIN - TAZOBACTAM arm will receive an initial 4g bolus of PIPERACILLIN - TAZOBACTAM and a 16g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. |
| CEFEPIME | Active comparator | Drug: CEFEPIMEAfter enrollment, patients of CEFEPIME arm will receive an initial 2g bolus of CEFEPIME and a 6g continuous infusion per day, during 48 hours, without modification of rhythm and dose according to renal function. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Septic shock
- Meropenem, piperacillin-tazobactam or cefepime started after enrollment
Key exclusion criteria (3 listed)
- Pregnancy
- Central nervous system infection
- Burns
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 |
|---|---|---|
| MEROPENEMAdministration of MEROPENEM according to a protocol of extended infusion defining dose and duration of infusion. | Drug | MEROPENEM |
| PIPERACILLIN-TAZOBACTAMAdministration of PIPERACILLIN-TAZOBACTAM according to a protocol of continuous infusion defining dose and duration of infusion. | Drug | PIPERACILLIN-TAZOBACTAM |
| CEFEPIMEAdministration of CEFEPIME according to a protocol of continuous infusion defining dose and duration of infusion. | Drug | CEFEPIME |
Primary outcome
Proportion of patients achieving the PK/PD target
Time frame: First 48 hours
Proportion of patients achieving the target of 100% of 48 first hours of treatment above 4 time the upper critical breakpoint for Pseudomonas Aeruginosa
1 secondary outcome
All cause mortality
Time frame: 28th day
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 16 Jan 2025.
- Results publication: PubMed 20594297Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Wittebole X, De Backer D, Layeux B, Wallemacq P, Vincent JL, Jacobs F. Insufficient beta-lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14(4):R126. doi: 10.1186/cc9091. Epub 2010 Jul 1.
- Derived from this study: PubMed 34768176Winiszewski H, Despres C, Puyraveau M, Lagoutte-Renosi J, Montange D, Besch G, Floury SP, Chaignat C, Labro G, Vettoretti L, Clairet AL, Capellier G, Vivet B, Piton G. beta-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study. J Crit Care. 2022 Feb;67:141-146. doi: 10.1016/j.jcrc.2021.10.023. Epub 2021 Nov 9.
- Individual participant dataSharing planned: Undecided
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Sepsis
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MEROPENEM, PIPERACILLIN-TAZOBACTAM and CEFEPIME in people with Septic Shock, run by Centre Hospitalier Universitaire de Besancon 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 2 inclusion and 3 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 16 Jan 2025. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Proportion of patients achieving the PK/PD target (time frame: First 48 hours). 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 NCT02820987, 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 16 Jan 2025.