Ignite Creation Date:
2024-05-05 @ 4:53 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00337714
Status:
COMPLETED
Last Update Posted:
2011-05-16
First Post:
2006-06-14
Brief Title:
Comparison of Central Venous Catheters With Silver Nanoparticles Versus Conventional Catheters
Sponsor:
Catholic University of the Sacred Heart
Organization:
Catholic University of the Sacred Heart
Study Overview
Official Title:
A Parallel Randomized Multicenter Comparison of Triple Lumen Central Venous Catheters Impregnated With Silver Nanoparticles AgTive Versus Conventional Catheters in Intensive Care Unit Patients
Status:
COMPLETED
Status Verified Date:
2008-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NanoAgCVC
Brief 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 andor 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
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
Detailed 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 grouptreatment 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 units 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 382 or 365C 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 19772961305-1309 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 005 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
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 grouptreatment 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 units 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 382 or 365C 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 19772961305-1309 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 005 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None