PeritonitisPhase 1NCT03790176
ZAVI APD ELF Protocol v2.2
A Phase 1 study testing Intravenous Infusion in people with Peritonitis and Pneumonia, run by Markus Zeitlinger at 1 site in Austria.
Trial summary
CAZ/AVI is a new antibiotic drug that is meant to be used for various indications including cIAI and nosocomial pneumonia. To date, limited data exists on PK of CAZ/AVI in patients undergoing peritoneal dialysis as well as on penetration of CAZ/AVI in ELF of critically ill patients. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Peritonitis, Pneumonia
- What is being tested?
- Intravenous Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteAustria
- Study dates
- 1 Oct 2018to Dec 2022
- Phase
- Phase 1
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged between 18 and 85 years undergoing automated peritoneal dialysis (APD)
- Written informed consent given after being provided detailed information about the nature, risks, and scope of the clinical study as well as the expected desirable and adverse effects of the drug
- No legal incapacity and/or other circumstances rendering the subject unable to understand the nature, scope and possible consequences of the study
- Age above 18 years
- Intubated patients admitted to an intensive care unit of the Vienna general hospital (AKH) participating in this study
- Sequential organ failure assessment (SOFA) score > 6 at study inclusion
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- Clinical diagnosis of nosocomial pneumonia or VAP
- Body mass index (calculated from measured or estimated body weight and height) between 18 and 40
- Therapy with CAZ/AVI at a dosage of 2g/0.5g three times daily (indication at the discretion of the treating physicians)
Who cannot join
- Known allergy or hypersensitivity against study drug or other beta-lactam antibiotics
- History of severe allergic or anaphylactic reactions to any medication
- Any systemic infection
- Peritonitis or catheter-related infection which required antibiotic treatment within 2 months prior to the start of the study
- Pregancy or, in case of women of child-bearing potential, lack of willingness to apply adequate contraception measures during study period
- Haemoglobin below 9 g/dl
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- Other objections to participate in the study in the opinion of the investigator
- Known allergy or hypersensitivity against study drug or other beta-lactam antibiotics
- Any disease considered relevant for proper performance of the study, or risks to the patient, at the discretion of the investigator
- Impaired renal function denoted by an estimated GFR of <50 mL/min according to Cockroft-Gault at study inclusion
- Requiring hemofiltration or hemodialysis
- Pregnancy
- Other factors that preclude study participation in the opinion of the investigator
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna
Vienna, 1090
Markus Zeitlinger, MD, 0043140400 ext. 29810, klin-pharmakologie@meduniwien.ac.at
About this study
Official title: Plasma, ELF and Intraperitoneal Pharmacokinetics of Ceftazidime/Avibactam in Critically Ill and Peritoneal Dialysis Patients
CAZ/AVI is a new antibiotic drug that is meant to be used for various indications including cIAI and nosocomial pneumonia. To date, limited data exists on PK of CAZ/AVI in patients undergoing peritoneal dialysis as well as on penetration of CAZ/AVI in ELF of critically ill patients. The present study is carried out to determine target site PK of CAZ/AVI in these two populations, in order to contribute to a more complete understanding of the drug's penetration to its site of action.
Read the detailed description
Ceftazidime/Avibactam (CAZ/AVI) is a novel antibiotic drug that has recently become available. It consists of a β-lactam/β-lactamase fixed drug combination with an almost exclusively Gram-negative spectrum and is indicated for the treatment of:
- complicated intra-abdominal infections (cIAI)
- complicated urinary tract infection (cUTI), including pyelonephritis
- hospital-acquired pneumonia including ventilator-associated pneumonia (VAP)
- infections due to aerobic Gram-negative organisms in patients with limited treatment options.
It is common knowledge that in anti-infective therapy, sufficient drug delivery to the target site is essential for antimicrobial efficacy and prevention of bacterial resistance. Based on this premise, the present exploratory trial will focus on the pharmacokinetics (PK) of CAZ/AVI in two patient populations:
PART A will investigate PK of CAZ/AVI in plasma and peritoneal dialysis fluid of patients undergoing automated peritoneal dialysis (APD). After a single intravenous dose of the drug PK sampling of CAZ/AVI will be performed in plasma and in peritoneal dialysis fluid, respectively. On the one hand, this will help to assess intraperitoneal exposure to CAZ/AVI after intravenous administration. This information might be of crucial importance for patients with infections localized in the peritoneal space. On the other hand, this study will show whether and to which extent CAZ/AVI is cleared from the bloodstream after intravenous administration in patients undergoing APD and receiving CAZ/AVI as treatment of other systemic infections, e.g. nosocomial pneumonia. Both aspects will improve current information on CAZ/AVI PK in peritoneal dialysis.
PART B will determine steady-state plasma and epithelial lining fluid (ELF) concentrations of CAZ/AVI in critically ill patients receiving the drug for treatment of nosocomial pneumonia (including VAP) at the discretion of their treating physicians. Penetration of CAZ/AVI into ELF has already been assessed in healthy volunteers and amounted roughly to 30% of plasma exposure. However, several physiological factors determining the amount of drug eventually recovered in ELF might be altered in critical illness (hemodynamics, binding to plasma and/or tissue proteins, local inflammation processes etc). Thus, PK of CAZ/AVI in lungs of critically ill patients might significantly differ from healthy volunteers, and deriving ELF exposure solely from plasma pharmacokinetics might not be entirely reliable in this circumstance. Still, considering the premise mentioned above, this issue is of crucial importance. The present study will help to assess whether CAZ/AVI reaches its target site (for the indication of nosocomial pneumonia) in critically ill patients to a sufficient degree.
Taken together, the information retrieved by this study will contribute to a better understanding of CAZ/AVI's disposition in target compartments of two patient populations and corroborate (or challenge) current dosing recommendations.
- Conditions
- Peritonitis, Pneumonia
- Being tested
- Intravenous Infusion
- Medical subject headings
- Peritonitis, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous InfusionDrug
see arm/group description. NO INTERVENTION IN STUDY GROUP B! PATIENTS OF GROUP B WILL RECEIVE CAZ/AVI INDEPENDENTLY FROM STUDY PARTICIPATION BASED ON DECISION OF THEIR TREATING PHYSICIAN
| Study group | Role | What they receive |
|---|---|---|
| A - patients on automated peritoneal dialysis | Other | each of n=8 patients will receive one single intravenous infusion of ceftazidime/avibactam (CAZ/AVI) 2g/0.5g over two hours. Subsequently, PK of CAZ/AVI will be determined in plasma and peritoneal dialysis fluid (and urine, if applicable) at protocol-defined time points over 24 hours. Receives: Drug: Intravenous Infusion |
| B - critically ill patients with pneumonia | Other | following one intravenous dose of 2g/0.5g CAZ/AVI (which patients will receive based on clinical indication by their treating physician), PK of CAZ/AVI will be determined at protocol-defined time points over one dosing interval in plasma and in epithelial lining fluid (ELF). Receives: Drug: Intravenous Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration time curve (AUC) from 0 to 8 hours (AUC0-8)
Measured: on study days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2018
- Study start1 Oct 2018
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PeritonitisStudies 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 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- group A - patients on automated peritoneal dialysis group B - critically ill patients with pneumonia
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Markus Zeitlinger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Markus Zeitlinger, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03790176
- Sponsor's protocol ID
- Version 2.2 April 19, 2018
- Status last verified
- Aug 2021
- First submitted
- 27 Dec 2018
- Last updated
- 8 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma, ELF and Intraperitoneal Pharmacokinetics of Ceftazidime/Avibactam in Critically Ill and Peritoneal Dialysis Patients
- ClinicalTrials.gov ID
- NCT03790176
- Acronym / sponsor ID
- Version 2.2 April 19, 2018
- Conditions
- Peritonitis, Pneumonia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Markus ZeitlingerUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 31 Dec 2018 (actual)
- 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.
CAZ/AVI is a new antibiotic drug that is meant to be used for various indications including cIAI and nosocomial pneumonia. To date, limited data exists on PK of CAZ/AVI in patients undergoing peritoneal dialysis as well as on penetration of CAZ/AVI in ELF of critically ill patients. The present study is carried out to determine target site PK of CAZ/AVI in these two populations, in order to contribute to a more complete understanding of the drug's penetration to its site of action.
Detailed description
Ceftazidime/Avibactam (CAZ/AVI) is a novel antibiotic drug that has recently become available. It consists of a β-lactam/β-lactamase fixed drug combination with an almost exclusively Gram-negative spectrum and is indicated for the treatment of:
- complicated intra-abdominal infections (cIAI)
- complicated urinary tract infection (cUTI), including pyelonephritis
- hospital-acquired pneumonia including ventilator-associated pneumonia (VAP)
- infections due to aerobic Gram-negative organisms in patients with limited treatment options.
It is common knowledge that in anti-infective therapy, sufficient drug delivery to the target site is essential for antimicrobial efficacy and prevention of bacterial resistance. Based on this premise, the present exploratory trial will focus on the pharmacokinetics (PK) of CAZ/AVI in two patient populations:
PART A will investigate PK of CAZ/AVI in plasma and peritoneal dialysis fluid of patients undergoing automated peritoneal dialysis (APD). After a single intravenous dose of the drug PK sampling of CAZ/AVI will be performed in plasma and in peritoneal dialysis fluid, respectively. On the one hand, this will help to assess intraperitoneal exposure to CAZ/AVI after intravenous administration. This information might be of crucial importance for patients with infections localized in the peritoneal space. On the other hand, this study will show whether and to which extent CAZ/AVI is cleared from the bloodstream after intravenous administration in patients undergoing APD and receiving CAZ/AVI as treatment of other systemic infections, e.g. nosocomial pneumonia. Both aspects will improve current information on CAZ/AVI PK in peritoneal dialysis.
PART B will determine steady-state plasma and epithelial lining fluid (ELF) concentrations of CAZ/AVI in critically ill patients receiving the drug for treatment of nosocomial pneumonia (including VAP) at the discretion of their treating physicians. Penetration of CAZ/AVI into ELF has already been assessed in healthy volunteers and amounted roughly to 30% of plasma exposure. However, several physiological factors determining the amount of drug eventually recovered in ELF might be altered in critical illness (hemodynamics, binding to plasma and/or tissue proteins, local inflammation processes etc). Thus, PK of CAZ/AVI in lungs of critically ill patients might significantly differ from healthy volunteers, and deriving ELF exposure solely from plasma pharmacokinetics might not be entirely reliable in this circumstance. Still, considering the premise mentioned above, this issue is of crucial importance. The present study will help to assess whether CAZ/AVI reaches its target site (for the indication of nosocomial pneumonia) in critically ill patients to a sufficient degree.
Taken together, the information retrieved by this study will contribute to a better understanding of CAZ/AVI's disposition in target compartments of two patient populations and corroborate (or challenge) current dosing recommendations.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- group A - patients on automated peritoneal dialysis group B - critically ill patients with pneumonia
| Arm | Type | Receives |
|---|---|---|
| A - patients on automated peritoneal dialysis | Other | Drug: Intravenous Infusioneach of n=8 patients will receive one single intravenous infusion of ceftazidime/avibactam (CAZ/AVI) 2g/0.5g over two hours. Subsequently, PK of CAZ/AVI will be determined in plasma and peritoneal dialysis fluid (and urine, if applicable) at protocol-defined time points over 24 hours. |
| B - critically ill patients with pneumonia | Other | Drug: Intravenous Infusionfollowing one intravenous dose of 2g/0.5g CAZ/AVI (which patients will receive based on clinical indication by their treating physician), PK of CAZ/AVI will be determined at protocol-defined time points over one dosing interval in plasma and in epithelial lining fluid (ELF). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males or females aged between 18 and 85 years undergoing automated peritoneal dialysis (APD)
- Written informed consent given after being provided detailed information about the nature, risks, and scope of the clinical study as well as the expected desirable and adverse effects of the drug
- No legal incapacity and/or other circumstances rendering the subject unable to understand the nature, scope and possible consequences of the study
- Age above 18 years
- Intubated patients admitted to an intensive care unit of the Vienna general hospital (AKH) participating in this study
Key exclusion criteria (13 listed)
- Known allergy or hypersensitivity against study drug or other beta-lactam antibiotics
- History of severe allergic or anaphylactic reactions to any medication
- Any systemic infection
- Peritonitis or catheter-related infection which required antibiotic treatment within 2 months prior to the start of the study
- Pregancy or, in case of women of child-bearing potential, lack of willingness to apply adequate contraception measures during study period
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 |
|---|---|---|
| Intravenous Infusionsee arm/group description. NO INTERVENTION IN STUDY GROUP B! PATIENTS OF GROUP B WILL RECEIVE CAZ/AVI INDEPENDENTLY FROM STUDY PARTICIPATION BASED ON DECISION OF THEIR TREATING PHYSICIAN | Drug | A - patients on automated peritoneal dialysis, B - critically ill patients with pneumonia |
Primary outcome
Area under the concentration time curve (AUC) from 0 to 8 hours (AUC0-8)
Time frame: on study days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous Infusion in people with Peritonitis and Pneumonia, run by Markus Zeitlinger at 1 site in Austria.
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 9 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 8 Sep 2021. 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 Austria. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the concentration time curve (AUC) from 0 to 8 hours (AUC0-8) (time frame: on study days). 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 8 Sep 2021; AzTrials last refreshed its copy on 28 Oct 2026.