Ignite Creation Date:
2024-05-06 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 3:19 PM
Study NCT ID:
NCT06238297
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-20
First Post:
2024-01-25
Brief Title:
Rapid De-escalation of Anti-MRSA Therapy Guided by S Aureus Nares Screening in Case of Pneumonia
Sponsor:
University of Bari Aldo Moro
Organization:
University of Bari Aldo Moro
Study Overview
Official Title:
Rapid De-escalation of Anti-MRSA Therapy Guided by S Aureus Nares Screening in Case of Pneumonia SNAP Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
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:
SNAP
Brief Summary:
The current IDSAATS guidelines recommend Linezolid and Vancomycin for MRSA coverage in hospitalized patients with pneumonia which is common clinical practice in Italy However a nasal PCR-assay for MRSA has a high negative predictive value and can facilitate rapid antibiotic de-escalation thereby avoiding unnecessary anti-MRSA treatments The indiscriminate use of these drugs has contributed to the emergence of resistant S aureus strains and has led to significant adverse effects without providing any survival benefits Additionally it has increased hospital stays and associated costs The proposed study aims to use this diagnostic tool to shorten empirical anti-MRSA treatment duration in pneumonia patients focusing on reducing antimicrobial therapy days while measuring in-hospital mortality length of stay and adverse drug event incidence
Detailed Description:
BACKGROUND On the basis of current IDSAATS guidelines antimicrobial agents such as Linezolid and Vancomycin are commonly used in hospitalized patients as an empirical treatment in community acquired pneumonias CAPs particularly in hospital-acquired pneumonias HAPs and ventilator associated pneumonias VAPs suggesting the empiric use of such anti-MRSA agents for patients with specific risk factors eg recent hospitalization exposure to parenteral antibiotics andor previous isolation of these organisms in particular from the respiratory tract while obtaining culture data
According to the 2023 annual report of the European Antibiotic Resistance Surveillance System EARSS there is a high prevalence of MRSA throughout the European territory however even in countries with high endemicity the presence of MRSA has remained stable in the last years In Italy according to the National Antibiotic-Resistance Surveillance System AR-ISS in 2021 the percentage of blood isolates MRSA isolates showed a reduction 299 in the national territory standing however at 336 in the Puglia region a percentage higher than the European
In patients with pneumonia the nasal PCR-assay for MRSA has a high negative predictive value NPV with the crucial implication that a negative result can be used to guide the antibiotic de-escalation avoiding an improper empiric use of the anti-MRSA therapy Data supporting the clinical validity of the use of the nasal swab for MRSA as a diagnostic tool for pneumonia are robust in this regard as stated by the IDSAATS guidelines and supported by numerous retrospective studies anti-MRSA treatment can be avoided in case of negative result especially in non-severe CAP thus preventing the misuse of anti-MRSA drugs
The indiscriminate use of these drugs over time has considerably led to the selection of resistant strains of S aureus such as Vancomycin-intermediate Staphylococcus aureus VISA heterogeneous VISA hVISA and Vancomycin-resistant Staphylococcus aureus VRSA Furthermore the high risk of adverse events given by the empirical use of anti-MRSA drugs should also be noted including among others nephrotoxicity and ototoxicity with vancomycin and bone marrow suppression and peripheral neuropathy with linezolid without a gain in terms of survival and with longer hospitalization stays
In addition the systematic use of such drugs is associated with an increase in hospital costs where the PCR assay for MRSA has a relevant role According to a study conducted by the Stanford University in 2021 enabling antibiotic de-escalation within 24h its use has of facts led to a cost saving of vancomycin of 4033 per patient
On these assumptions it is clear that using the nasal swab for MRSA in pneumonia diagnosis avoids the use of expensive drugs giving a large impact on health costs while also reducing the risk of iatrogenic toxicity hospital stay days and the duration of ventilation in VAPs
The aim of our study is to implement the use of the nasal swab for MRSA as a diagnostic tool reducing the duration of the empirical anti-MRSA treatment in the population of hospitalized patients with pneumonia
METHODS AND PROCEDURES This will be a prospective randomized single-center controlled study conducted in the Azienda Consorziale Policlinico di Bari
The minimum sample size is 38 patients per group for a total of 76 subjects calculated assuming a standard deviation of 10 a power of 90 and a type I error of 5
The study will involve two phases a first phase of enrollment of the subjects with the collection of informed consent of the anamnestic and personal data a phase of randomization with consequent execution within 48h from the start of the anti-MRSA empirical therapy of the nasal swab for MRSA in the experimental group of patients In a second step the research assistants will continue the follow-up of the subject with cessation of the empiric treatment in case of negative result of the swab
The implementation of these steps will be ensured by the performance of the tasks foreseen for each unit Each clinical unit will
Enroll patients and collect demographic clinical and biochemical data at baseline as well as ensure their management according to guidelines and scientific evidence for the entire duration of the follow-up
Perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative
For both arms follow-up visits will be on day 2 5 7 14 and 28 relative to the enrollment visit day 0 At the control visits data will be collected on the clinical course of pneumonia and laboratory tests After discharge the visit can also be conducted by telephone
For more precision eligibility criteria and primary and secondary outcomes descriptions are fully detailed in the corresponding sections
TIMELINE The research project will have a duration of 12 months following the approval of the Ethics Committee of the University of BarI
STATISTICAL ANALYSIS The sample size is estimated based on the main outcome measure duration of antibiotic intake which the investigators assume to have an average of 10 days in the control group and 2 days in the experimental group Assuming a standard deviation of 10 a power of 90 and a type I error of 5 it is necessary to enroll a minimum of 34 patients per group thus a total of 68 patients in order to demonstrate a reduction from 10 to 2 days in the duration of antibiotic intake To this is added an estimated 10 of cases lost to follow-up resulting in a final sample size of 76 patients
The statistical analysis will be conducted according to the intention-to-treat approach In case of contamination between the two treatment groups which is considered unlikely in this case an analysis per protocol will also be performed and the conclusions of the study will take into account the results of both Numerical data will be summarized as mean and standard deviation while categorical data as absolute and relative frequency The two groups will be compared with the Students t-test numerical data and with the Chi-Square test or Fishers test categorical data The effects will be expressed as mean difference or relative risk accompanied by a 95 confidence interval All tests will be two-tailed and a p-value lower than 005 will be considered significant The statistical analysis will be carried out with R software version 43 R Foundation for Statistical Computing Vienna Austria
According to the 2023 annual report of the European Antibiotic Resistance Surveillance System EARSS there is a high prevalence of MRSA throughout the European territory however even in countries with high endemicity the presence of MRSA has remained stable in the last years In Italy according to the National Antibiotic-Resistance Surveillance System AR-ISS in 2021 the percentage of blood isolates MRSA isolates showed a reduction 299 in the national territory standing however at 336 in the Puglia region a percentage higher than the European
In patients with pneumonia the nasal PCR-assay for MRSA has a high negative predictive value NPV with the crucial implication that a negative result can be used to guide the antibiotic de-escalation avoiding an improper empiric use of the anti-MRSA therapy Data supporting the clinical validity of the use of the nasal swab for MRSA as a diagnostic tool for pneumonia are robust in this regard as stated by the IDSAATS guidelines and supported by numerous retrospective studies anti-MRSA treatment can be avoided in case of negative result especially in non-severe CAP thus preventing the misuse of anti-MRSA drugs
The indiscriminate use of these drugs over time has considerably led to the selection of resistant strains of S aureus such as Vancomycin-intermediate Staphylococcus aureus VISA heterogeneous VISA hVISA and Vancomycin-resistant Staphylococcus aureus VRSA Furthermore the high risk of adverse events given by the empirical use of anti-MRSA drugs should also be noted including among others nephrotoxicity and ototoxicity with vancomycin and bone marrow suppression and peripheral neuropathy with linezolid without a gain in terms of survival and with longer hospitalization stays
In addition the systematic use of such drugs is associated with an increase in hospital costs where the PCR assay for MRSA has a relevant role According to a study conducted by the Stanford University in 2021 enabling antibiotic de-escalation within 24h its use has of facts led to a cost saving of vancomycin of 4033 per patient
On these assumptions it is clear that using the nasal swab for MRSA in pneumonia diagnosis avoids the use of expensive drugs giving a large impact on health costs while also reducing the risk of iatrogenic toxicity hospital stay days and the duration of ventilation in VAPs
The aim of our study is to implement the use of the nasal swab for MRSA as a diagnostic tool reducing the duration of the empirical anti-MRSA treatment in the population of hospitalized patients with pneumonia
METHODS AND PROCEDURES This will be a prospective randomized single-center controlled study conducted in the Azienda Consorziale Policlinico di Bari
The minimum sample size is 38 patients per group for a total of 76 subjects calculated assuming a standard deviation of 10 a power of 90 and a type I error of 5
The study will involve two phases a first phase of enrollment of the subjects with the collection of informed consent of the anamnestic and personal data a phase of randomization with consequent execution within 48h from the start of the anti-MRSA empirical therapy of the nasal swab for MRSA in the experimental group of patients In a second step the research assistants will continue the follow-up of the subject with cessation of the empiric treatment in case of negative result of the swab
The implementation of these steps will be ensured by the performance of the tasks foreseen for each unit Each clinical unit will
Enroll patients and collect demographic clinical and biochemical data at baseline as well as ensure their management according to guidelines and scientific evidence for the entire duration of the follow-up
Perform a nasal swab for MRSA in patients in the experimental group and discontinue the empirical anti-MRSA therapy if the nasal swab result is negative
For both arms follow-up visits will be on day 2 5 7 14 and 28 relative to the enrollment visit day 0 At the control visits data will be collected on the clinical course of pneumonia and laboratory tests After discharge the visit can also be conducted by telephone
For more precision eligibility criteria and primary and secondary outcomes descriptions are fully detailed in the corresponding sections
TIMELINE The research project will have a duration of 12 months following the approval of the Ethics Committee of the University of BarI
STATISTICAL ANALYSIS The sample size is estimated based on the main outcome measure duration of antibiotic intake which the investigators assume to have an average of 10 days in the control group and 2 days in the experimental group Assuming a standard deviation of 10 a power of 90 and a type I error of 5 it is necessary to enroll a minimum of 34 patients per group thus a total of 68 patients in order to demonstrate a reduction from 10 to 2 days in the duration of antibiotic intake To this is added an estimated 10 of cases lost to follow-up resulting in a final sample size of 76 patients
The statistical analysis will be conducted according to the intention-to-treat approach In case of contamination between the two treatment groups which is considered unlikely in this case an analysis per protocol will also be performed and the conclusions of the study will take into account the results of both Numerical data will be summarized as mean and standard deviation while categorical data as absolute and relative frequency The two groups will be compared with the Students t-test numerical data and with the Chi-Square test or Fishers test categorical data The effects will be expressed as mean difference or relative risk accompanied by a 95 confidence interval All tests will be two-tailed and a p-value lower than 005 will be considered significant The statistical analysis will be carried out with R software version 43 R Foundation for Statistical Computing Vienna Austria
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None