ANZCTR - Registration

Please note that the ANZCTR website will be unavailable from 1:00pm until 2:00pm (AEST) on Thursday 10th of April for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.

With activity expected to increase on the ANZCTR again, there may be extended wait times while we process pending studies, with priority being given to those trials submitted in February. Thank you for your patience.

Reset your password and enable multi-factor authentication (MFA)

For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.

Go to the Login page, click ‘reset password’ and follow the instructions.
Check your email for the link to set a new password.
Create a new password that meets requirements.
Return to the Login page and enter your new password. A verification code will be sent to your email.
Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12616000167460

Ethics application status

Approved

Date submitted

7/01/2016

Date registered

10/02/2016

Date last updated

10/10/2017

Type of registration

Retrospectively registered

Titles & IDs

Public title

Antibiotic Concentration in Critically ill intensive care unit (ICU) patients in Sweden

Scientific title

Antibiotic Concentration in Critically ill ICU-patients in Sweden (ACCIS)

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

ACCIS

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Sepsis

Septic shock

Critical illness

Condition category

Condition code

Infection

Other infectious diseases

Intervention/exposure

Study type

Observational

Patient registry

True

Target follow-up duration

Target follow-up type

Days

Description of intervention(s) / exposure

Concentrations of cefotaxime, piperacillin-tazobactam, meropenem, ciprofloxacin, gentamicin, tobramycin, amikacin and vancomycin in the plasma will be assessed upon start of antibiotic therapy, in intensive care patients with suspected or verified infection. Blood samples will be taken twice daily for 3 days. Clinical data with impact on pharmacokinetics as well as microbiological results will be collected.

Intervention code [1]

Not applicable

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To assess if antibiotic concentrations in plasma are lower than those recommended in current international guidelines.

Timepoint [1]

Days 1-3 of antibiotic therapy.

Secondary outcome [1]

To assess if antibiotic concentrations in plasma are higher than those recommended in current international guidelines.

Timepoint [1]

Days 1-3 of antibiotic therapy.

Secondary outcome [2]

To find mechanistic explanations to variations in plasma antibiotic concentration in this group such as variations in renal function (eGFR), liver function (INR), plasma protein levels (plasma albumin), continuous renal replacement therapy (dose) etc.

Timepoint [2]

Days 1-3 antibiotic therapy.

Secondary outcome [3]

To relate plasma antibiotic concentration to the MIC values of the isolated bacteria from each patient with positive cultures.

Timepoint [3]

Days 1-3 of antibiotic therapy.

Eligibility

Key inclusion criteria

Intensive care patient with any severe suspected or verified infection requiring initiation of new antibiotic treatment.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Intermittent hemodialysis
Known pregnancy
Limitations of care

Study design

Purpose

Natural history

Duration

Cross-sectional

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Descriptive statistics

To show that 10% of the patients have lower plasma antibiotic concentration than current recommendations, at least 16 patients will have to be included for each 8 studied antibiotic agent for an alpha error of 0.05 and beta error of 0.8. Due to the risk of missing data, uneven distribution between groups etc we aim at including 150 patients i.e. 10% more than the sample size suggests.
To counteract uneven distribution between groups, an interim analysis will be performed after the inclusion of 75 patients to ensure that the distribution of patients is similar for the eight antibiotics studied. Inclusion for antibiotics with 16 or more patients included will be terminated.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

Actual

18/01/2016

Date of last participant enrolment

Anticipated

Actual

5/07/2017

Date of last data collection

Anticipated

Actual

3/09/2017

Sample size

Target

150

Accrual to date

Final

158

Recruitment outside Australia

Country [1]

Sweden

State/province [1]

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Uppsala-Orebro Regional Research Council

Address [1]

Uppsala-Orebro Regional Research Council 801 88 Gavle Sweden

Country [1]

Sweden

Funding source category [2]

Hospital

Name [2]

Uppsala university hospital research fund

Address [2]

Akademiska sjukhuset 751 85 Uppsala Sweden

Country [2]

Sweden

Primary sponsor type

University

Name

Uppsala university

Address

Department of Surgical Sciences
Anaesthesiology and Intensive Care
Uppsala University
Akademiska sjukhuset
751 85 Uppsala
Sweden

Country

Sweden

Secondary sponsor category [1]

Hospital

Name [1]

Uppsala university hospital

Address [1]

Akademiska sjukhuset 751 85 Uppsala Sweden

Country [1]

Sweden

Other collaborator category [1]

Hospital

Name [1]

Karlstad county hospital

Address [1]

Centralsjukhuset i Karlstad Rosenborgsgatan 652 30 Karlstad Sweden

Country [1]

Sweden

Other collaborator category [2]

Hospital

Name [2]

Eskilstuna county hospital

Address [2]

Malarsjukhuset Kungsvagen 34 633 49 Eskilstuna Sweden

Country [2]

Sweden

Other collaborator category [3]

Hospital

Name [3]

Vasteras county hospital

Address [3]

Vastmanlands sjukhus Vasteras 721 89 Vasteras Sweden

Country [3]

Sweden

Other collaborator category [4]

Hospital

Name [4]

Gavle county hospital

Address [4]

Gavle sjukhus Lasarettsvagen 5 803 24 Gavle Sweden

Country [4]

Sweden

Other collaborator category [5]

Hospital

Name [5]

Karolinska University Hospital Huddinge

Address [5]

Karolinska Universitetssjukhuset Huddinge Halsovagen, Flemingsberg 141 86 Stockholm Sweden

Country [5]

Sweden

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Regional Ethical Review Board, Uppsala

Ethics committee address [1]

Drottninggatan 4
753 09 Uppsala
Sweden

Ethics committee country [1]

Sweden

Date submitted for ethics approval [1]

26/03/2015

Approval date [1]

03/09/2015

Ethics approval number [1]

Dnr 2015/135

Summary

Brief summary

Background
Antibiotic therapy has the major impact on morbidity and mortality in severe sepsis and septic shock (Kumar, Roberts et al. 2006; Bagshaw, Lapinsky et al. 2009). Rapid killing of bacteria is considered important to limit the infection and systemic inflammatory response. Pharmacokinetic data for most antibiotics are obtained in healthy human volunteers.  Hence, it is unclear if adequate antibiotic concentrations in plasma are achieved in critically ill patients with infections, especially on the first day of treatment when benefits of adequate dosed antibiotics are greatest. This is unfortunate, since the outcome in ICU patients depends on early, accurate and adequately dosed antibiotic treatment. Underdosing antibiotics leads to the no or limited effect against infectious agents with the risk of lack of infection control as well as risk of emergence of multi-resistant strains. Overdosing antibiotics increases the risk of toxicity without providing additional benefit. 
There are several reasons for variations in drug concentration in ICU. Large changes in total body water may be seen due to intravenous fluids given during resuscitation (Liu, Thompson et al. 2011). Moreover, changes are seen in plasma protein levels (Investigators, Finfer et al. 2011) permeability between the different compartments, liver function, (Macnab, Macrae et al. 1986) renal function (White, Hassoun et al. 2013) and renal tubular function (Wen, Peng et al. 2011). In addition, critically ill patients treated with continuous renal replacement therapy (CRRT) in severe renal impairment that alters the excretion of the drugs with predominantly renal clearance (Lau, Kronfol et al. 1987).
Thus, to date it is unknown what proportion of the ICU patients have adequate plasma concentrations of antibiotics, whether antibiotic concentrations change during the first days and if the pharmacokinetics of these drugs is affected by the critical illness and / or intensive care.
Hypothesis
Plasma concentrations of antibiotics in ICU patients during the first 72 hours after initiation of treatment are too low to provide adequately dosed antibacterial therapy. 
Method
In a prospective multicenter study, concentrations of cefotaxime, piperacillin-tazobactam, meropenem, ciprofloxacin, gentamicin, tobramycin, amikacin and vancomycin in the plasma will be measured twice daily for 3 days after the initiation of treatment in intensive care patients with suspected infection. Participating centers are: the general ICU, the cardiothoracic ICU and the burns ICU at Uppsala university hospital, and general ICUs at County hospitals in Eskilstuna, Vasteras, Karlstad, and Gavle, as well as the general ICU at Karolinska University Hospital Huddinge. Demographic, clinical, laboratory and microbiological data will be collected.  Antibiotic concentrations in each patient with positive cultures will be compared with the MIC for the isolated bacteria from the same patient.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Miklos Lipcsey

Address

Department of Surgical Sciences Anaesthesiology and Intensive Care Uppsala University Hospital Akademiska sjukhuset 751 85 Uppsala Sweden

Country

Sweden

Phone

+46 - 18 - 611 96 60

Fax

[email protected]

Contact person for public queries

Name

Miklos Lipcsey

Address

Department of Surgical Sciences Anaesthesiology and Intensive Care Uppsala University Hospital Akademiska sjukhuset 751 85 Uppsala Sweden

Country

Sweden

Phone

+46 - 18 - 611 96 60

Fax

[email protected]

Contact person for scientific queries

Name

Miklos Lipcsey

Address

Department of Surgical Sciences Anaesthesiology and Intensive Care Uppsala University Hospital Akademiska sjukhuset 751 85 Uppsala Sweden

Country

Sweden

Phone

+46 - 18 - 611 96 60

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Low attainment to PK/PD-targets for beta-lactams in a multi-center study on the first 72 h of treatment in ICU patients.	2022	https://dx.doi.org/10.1038/s41598-022-25967-9
Embase	Population pharmacokinetics of cefotaxime in intensive care patients.	2022	https://dx.doi.org/10.1007/s00228-021-03218-6
Embase	Swedish multicentre study of target attainments with beta-lactams in the ICU: which MIC parameter should be used?.	2023	https://dx.doi.org/10.1093/jac/dkad327

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically