ZAVI APD ELF Protocol v2.2

  • STATUS
    Recruiting
  • days left to enroll
    80
  • participants needed
    20
  • sponsor
    Markus Zeitlinger
Updated on 28 February 2022
pneumonia
body mass index
antibiotic therapy
antibiotics
critical illness
dialysis
nosocomial pneumonia

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. 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.

Description

Ceftazidime/Avibactam (CAZ/AVI) is a novel antibiotic drug that has recently become available. It consists of a -lactam/-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.

Details
Condition Peritonitis, Pneumonia
Treatment Intravenous Infusion
Clinical Study IdentifierNCT03790176
SponsorMarkus Zeitlinger
Last Modified on28 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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)

Exclusion Criteria

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note