Condition category
Infections and Infestations
Date applied
02/01/2012
Date assigned
20/01/2012
Last edited
20/01/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
How well the antibiotic meropenem works depends on the dose used. The aim of this study was to compare the benefits of continuous infusion of meropenem against bolus administration (large dose given by injection in bloodstream to achieve the desired level rapidly), in critically ill patients, with severe infection.

Who can participate?
Patients aged 18 years or older (both men and women), admitted to the intensive care unit (ICU) of the university hospital, who suffered from severe infection .

What does the study involve?
Comparing continuous infusion of meropenem versus intermittent administration of meropenem given in higher daily dose. Patients were were randomly allocated to the Infusion group or the Bolus group.

What are the possible benefits and risks of participating?
We presumed that continuous infusion of meropenem could provide the same or better clinical and microbiological efficacy than intermittent administration of meropenem given in higher daily dose.
There were no additional risks in both groups.

Where is the study run from?
Department of Anesthesiology and Intensive Care Medicine at Charles University teaching hospital in Plzen, Czech Republic.

When is study starting and how long is it expected to run for?
The study started on 01/10/2007 and ended on 30/04/2010.

Who is funding the study?
Czech Ministry of Education (project ref: MSM0021620819).

Who is the main contact?
Dr Ivan Chytra
chytra@fnplzen.cz

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ivan Chytra

ORCID ID

Contact details

Department of Anesthesia and Intensive Care
Charles University Teaching Hospital
Alej Svobody 80
Plzen
30460
Czech Republic

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized prospective single center study

Acronym

Study hypothesis

Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration (MIC) of pathogens. In conventional bolus dosing regimens serum concentrations of meropenem between doses can fall to lower concentrations than MIC of less susceptible pathogens. We presume that continuous infusion of meropenem can provide the same or better clinical and microbiological efficacy than intermittent administration of meropenem given in higher daily dose.

Ethics approval

Local Research Ethics Committee of University Hospital in Plzen, 17 May 2007

Study design

Single-center prospective randomized open-label comparative study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Critically ill patients with severe infection

Intervention

Patients admitted to the intensive care (ICU) of university hospital who suffered from severe infection and received meropenem were randomized either in the Infusion group or in the Bolus group.

Patients in the Infusion group received loading dose of 2g of meropenem followed by continuous infusion of 4g of meropenem over 24 hours.

Patients in the Bolus group were given 2g of meropenem over 30 minutes every 8 hours.

Clinical and microbiological outcome, meropenem-related length of ICU and hospital stay, meropenem-related length of mechanical ventilation, duration of meropenem treatment, total dose of meropenem, ICU and in-hospital mortality, safety and cost effectiveness were assessed.

Patients were followed up to hospital discharge.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. Clinical and microbiological efficacy of meropenem therapy were evaluated at the end of meropenem therapy
Clinical response was evaluated at the end of therapy as treatment success or failure. Clinical success was defined as complete or partial resolution of leukocytosis, temperature, and clinical signs and symptoms of infection. Cure was defined as complete resolution of all acute signs and symptoms of infection, with no new signs or symptoms associated with the original infection. Patients who retained evidence of infection but demonstrated a reduction of the majority of the clinical signs and symptoms of infection and no new or worsened signs associated with the original infection were classified as improved. For the purpose of statistical analysis, patients meeting the definitions of cured and improved were combined and defined as clinical successes. Failure consisted of any of the following:
1.1. Persistence or progression of signs and symptoms of infection
1.2. Development of new clinical findings consistent with active infection
1.3. Death from infection

2. Microbiological outcome was assigned one of the following categories: eradication, presumed eradication, persistence, presumed persistence, resistance or unevaluable. Eradication was defined as elimination of the pathogen from the site of isolation. Presumed eradication consisted of absence of appropriate material for culture or absence of results of control microbiological tests coupled with clinical improvement after a pathogen was initially isolated. Three possible outcomes were defined collectively as persistence: verified persistence (failure to eradicate the original pathogen from the site of isolation after completion of therapy), presumed persistence (absence of appropriate material for culture or absence of results of control microbiological tests coupled with lack of clinical improvement after a pathogen was initially isolated) and development of resistance during therapy. Patients without cultures or evident pathogens from the presumed site of infection were deemed unevaluable.The categories of eradication and presumed eradication were combined and defined as microbiologic success. Persistence was designated as microbiologic failure.

Secondary outcome measures

1. Meropenem-related length of mechanical ventilation
2. Meropenem-related length of ICU and hospital stay (LOS)
3. ICU and in-hospital mortality
4. Duration of meropenem treatment
5. The total dose of meropenem
6. Safety and cost effectiveness of both dosing regimens

Overall trial start date

01/10/2007

Overall trial end date

30/04/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients aged 18 years and over
2. Admitted to the interdisciplinary Intensive Care Unit (ICU) between September 2007 and May 2010
3. Had suffered from severe infection and received meropenem with predicted duration of treatment for at least 4 days at the admission or during the ICU stay
4. Types of infections include:
4.1. Abdominal
4.2. Respiratory
4.3. Skin
4.4. Soft tissue
4.5. Bloodstream
4.6. Central nervous system
4.7. Urinary tract
4.8. Other sources of infections

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Target number of participants was 240

Participant exclusion criteria

1. Age younger than 18 years
2. Pregnancy
3. Acute or chronic renal failure with glomerular filtration rate lower than 0.5 ml/s
4. Immunodeficiency or immunosuppressant medication
5. Neutropenia
6. Hypersensitivity or allergy to meropenem

Recruitment start date

01/10/2007

Recruitment end date

30/04/2010

Locations

Countries of recruitment

Czech Republic

Trial participating centre

Department of Anesthesia and Intensive Care
Plzen
30460
Czech Republic

Sponsor information

Organisation

Charles University Teaching Hospital Plzen (Czech Republic)

Sponsor details

Department of Anesthesia and Intensive Care
Alej Svobody 80
Plzen
304 60
Czech Republic
+420 377 104 384
chytra@fnplzen.cz

Sponsor type

Hospital/treatment centre

Website

http://lfp.cuni.cz/

Funders

Funder type

Government

Funder name

Czech Ministry of Education (Czech Republic) ref: MSM0021620819

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes