Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00337714 |
| Other study ID # |
60% MURST no. 7020119-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
June 14, 2006 |
| Last updated |
May 13, 2011 |
| Start date |
July 2006 |
| Est. completion date |
September 2008 |
Study information
| Verified date |
September 2008 |
| Source |
Catholic University of the Sacred Heart |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Italy: National Institute of Health |
| Study type |
Interventional
|
Clinical Trial Summary
Bloodstream infections are common in Intensive Care Units (ICUs). The need of a central
venous line increases the risk of bacteremia and central venous catheter (CVC) related
infections. The use of catheters coated and/or impregnated with different antimicrobial
agents has been proposed to reduce the risk of such infections. However, results obtained so
far did not reach enough clinical relevance to consider these medicated catheters as a valid
alternative to the conventional ones.
The aim of this comparative randomized study is to assess the ability of recently developed
silver ion-releasing central venous catheters in preventing associated infections in
comparison with the conventional ones.
Experimental groups are defined as follows:
- Group A: patients treated with standard, triple lumen, non medicated catheters
- Group B: patients treated with triple lumen catheters impregnated with silver
nanoparticles
Description:
RATIONALE
Central venous catheter (CVC) infections are one of the major causes of infections acquired
in intensive care unit (ICU) patients. About 25% of bloodstream infections recorded in ICUs
are secondary to proven catheter-related infections and up to 80% of the so-called primary
bacteraemia may be caused by catheters. Pittet et al. have estimated that nosocomial
bloodstream infection, irrespective of its source, was associated with an overall 35%
attributable mortality and a prolonged hospital stay of 32 days, including 8 days in the
ICU. Prevention of catheter-related infections is a priority for infection control programs.
Clear preventive measures include strict barrier precautions during insertion and careful
aseptic techniques during subsequent manipulations of catheters. Other preventive measures,
including the use of catheters specifically designed to inhibit microbial colonisation, such
as antimicrobial-coated catheters, are not universally accepted or recommended for routine
use, also due to their high cost. Previous trials have demonstrated a 50% risk reduction of
infection rates when using antiseptic-coated catheters; however, their efficacy in reducing
catheter related bloodstream infections is still unclear. A new generation of silver
nanoparticle impregnated CVCs (Logicath AgTive®, Medex Medical INC., UK), has become
recently available, but no clinical trial documenting their activity in preventing microbial
colonization of catheters has been carried out so far. In this study, we want to assess the
ability of this new generation catheters to prevent short-term (< 28 days) catheter-related
infections in critically ill patients, in comparison with conventional untreated catheters.
STUDY POPULATION
All consecutively admitted critically ill patients needing central venous catheterization
for more than 5 days.
TRIAL OBJECTIVE AND PURPOSE
The objective of this study is to test the ability of these new medicated catheters, to
reduce the risk of Central Venous Catheter Related Infections (CVCRI) in ICU patients. CVCRI
is defined as a positive culture from the catheter when hemoculture is concurrently positive
for the same microbial strain for at least two consecutive times.
TRIAL DESIGN
Study Design
This is a randomized, open, controlled, parallel multicenter study involving 5 Italian ICUs
and the supporting clinical microbiology laboratories under the supervision of Prof. Massimo
Antonelli, for the clinical issues and Prof Gianfranco Donelli, for the microbiology issues.
Statistical evaluation of the data will be under the responsibility of Dott. Andrea De
Gaetano, belonging to the Biomatematic Laboratory of the Italian National Research Council
(CNR-IASI).
Endpoints
The primary end-point is the difference in raw percentage occurrence of CVCRI (on a patient
basis) between groups A and B.
The secondary end-point are the infection-free time and the probability of CVCRI as a
function of multiple predictors.
METHODS
Randomization and blinding
An Internet-based randomization scheme, stratified by center, age and gender will be
employed, indicating the allocated treatment at the moment of enrollment. The randomization
procedure will require that when guide wire exchange is performed, a catheter from the same
allocation group (medicated or not medicated) is used. The treatment will be open to the
physician performing the procedure, and data collection will indicate group membership as A
and B in random order. While the data manager will hold the key to the group/treatment
associations, both the adjudication committee members (deciding on database record freezing)
and the statisticians performing the analyses will be blinded to treatment allocation.
Insertion and maintenance of catheters
Recommendations will be provided to study centers to comply with maximal barrier precautions
during insertion and repositioning of catheters, if indicated. A transparent, semipermeable
dressing, will be provided to all the participating ICUs to be used after insertion, to
allow daily inspection of the insertion site. Subsequent dressings will be carried out as
clinically indicated, at 2 to 5 days intervals. Line tubing and three-way stopcocks will be
changed on the basis of each unit's protocol at 1 to 3 days intervals, although changing
these after each blood product transfusion and following the administration of lipid
solutions will be required.
The catheter will be kept in place as long as required in the absence of complications.
Catheters will be removed when no longer required, or because of malfunction, when suspicion
of infection or otherwise unexplained bloodstream infection occurs; and in the presence of
gross inflammation or pus at the catheter insertion site. In situ treatment of catheter
infection will not be allowed.
Data recorded
The following information will be recorded upon inclusion: age, sex, date of hospital
admission and to the intensive care unit; underlying disease and severity (McCabe class);
admission category (medical, surgical, whether or not scheduled, or trauma), diagnosis and
primary organ failure on ICU admission. The severity score SAPS II, organ dysfunction and
SOFA score will also be recorded, as well as the presence of an active infection focus,
ongoing antibiotic therapy, and presence of other intravascular devices. Patients will be
followed up to 48 hours after catheter removal. Data recorded will include: a) Mechanical
complication occurring during insertion (number of venipunctures, arterial puncture,
hematoma, pneumothorax); b) presence of local signs suggesting infection (erythema at the
catheter skin entry site, scored as 0: absence; 1+: <5mm; 2+: 5-10mm; 3+: >10mm; presence of
induration or purulence); c) presence of a systemic inflammatory response syndrome or of
symptoms characterizing severe sepsis; d) Presence of other documented infection ; e) other
intravascular devices in place or inserted each day; f) dressing changes; g) Results of
blood and catheter-tip cultures, and of other clinically significant microbiological
samplings; h) antibiotics administered.
Microbiological data
Blood cultures will be obtained when temperature is > 38°2 or < 36°5C. Diagnostic samples of
any other suspected infection foci will be taken as clinically indicated. Upon catheter
removal, the intravascular catheter tip will be cultured using the semi quantitative culture
described by Maki et al. (Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method
for identifying intravenous-catheter-related infection. N Engl J Med 1977;296:1305-1309).
This technique involves rolling of the catheter distal tip on Agar plate and reading the
high-density colonization on a semiquantitative culture (more than 15 colonies on each
plate).
Inclusion Criteria
Patients will be eligible when insertion of a central venous catheter (CVC) at a new site
(subclavian or internal jugular) has to be planned for therapy or monitoring of at least
3-day duration.
Exclusion Criteria Age below 18 years and all patients with a history of failed
catheterization attempts or the need for catheterization at a site of previous surgery,
skeletal deformity, or scarring.
Data analysis
A Clinical Evaluation (Adjudication) Committee composed of the two coordinating
investigators (Prof. Massimo Antonelli and Prof. Gianfranco Donelli) and the statistician
(Dr. Andrea De Gaetano) will assess, blindly with respect to the randomization group, the
evaluability of catheters and the classification of all episodes of bloodstream infection
and of catheters having a positive culture, according to the above definitions. Catheters
will be excluded from the analysis when insertion fails. Catheters that have not been
adequately followed-up until the time of removal (transfer to another unit or hospital) will
be censored on the last day of follow-up in the ICU and classified by the Committee as
infected or uninfected, using the data available up to the last day of follow-up and any
bacteriological data subsequently received.
ASSESSMENT OF SAFETY
Adverse Events
Complications of the procedure will be classified according to a Complications Diagnosis
Dictionary. Text comments will be added to the recordings as appropriate. Descriptive
analysis of the complications as well as comparison of complication rates (overall and by
family of most frequent complications) will be obtained.
STATISTICS
Sample Size and Power Computation
The catheter-related infection rate was estimated at 10% in the conventional catheter group.
Assuming a 50% relative reduction (to 5%) in the silver impregnated CVC treated group, the
number of patients needed (or equivalently the number of patients enrolled, assuming an
attrition rate of 10%) for each treatment group in order to reach the desired statistical
power is reported below, assuming a Type I error level of 0.05 and depending on the
significance level and the number of tails of the statistical test.
Two-tailed tests will be considered throughout. A power of 80% will be considered
sufficient. Therefore, 472 patients per group should be enrolled.
