Ignite Creation Date:
2024-05-06 @ 3:15 AM
Last Modification Date:
2024-10-26 @ 11:31 AM
Study NCT ID:
NCT02249273
Status:
COMPLETED
Last Update Posted:
2017-10-09
First Post:
2014-09-22
Brief Title:
Diagnostic Tools in Patients With a Suspected Urinary Tract Infection in Primary Care
Sponsor:
University of Copenhagen
Organization:
University of Copenhagen
Study Overview
Official Title:
Diagnostic Process in Patients With a Suspected Urinary Trcat Infection in Danish Primary Care Impact on Appropriate Use of Antibiotics and Patients Recovery
Status:
COMPLETED
Status Verified Date:
2017-10
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:
None
Brief Summary:
Background Inappropriate use of antibiotics is one of the main causes for the increase of antibiotic resistance strains In Denmark general practice accounts for 90 of all prescribed antibiotics and one of the most common reasons for prescribing antibiotics is the suspicion of a urinary tract infection UTI The use of point-of-care test is meant to decrease the uncertainty about the bacterial origin of the symptoms however there is a paucity of knowledge about the validity of the different diagnostic approaches thus impacting on the proper use of antibiotics
Objective To assess the diagnostic validity of different diagnostic approaches in patients with a suspected urinary tract infection and assess the impact on appropriate use of antibiotics
Methods 70 practices at the capital region will consecutively include 15-20 patients The inclusion criteria of the patients comprise a Suspected Urinary tract infection b 18 years of age c patient consulting during office hours Data at patient and GP level will be gathered
16 diagnostic approaches will be compared and proper use of antibiotics will be assessed as a two-step process The first step is the decision made during the consultation and the second step is the decision made after the consultation Sensitivity specificity and predictive values will be measure for each diagnostic approach using urine culture as a gold standard The impact on proper use of antibiotics will be assessed in a hierarchical multivariable logistic model
Objective To assess the diagnostic validity of different diagnostic approaches in patients with a suspected urinary tract infection and assess the impact on appropriate use of antibiotics
Methods 70 practices at the capital region will consecutively include 15-20 patients The inclusion criteria of the patients comprise a Suspected Urinary tract infection b 18 years of age c patient consulting during office hours Data at patient and GP level will be gathered
16 diagnostic approaches will be compared and proper use of antibiotics will be assessed as a two-step process The first step is the decision made during the consultation and the second step is the decision made after the consultation Sensitivity specificity and predictive values will be measure for each diagnostic approach using urine culture as a gold standard The impact on proper use of antibiotics will be assessed in a hierarchical multivariable logistic model
Detailed Description:
Background
The latest report from the Staten Serum Institute SSI1 showed that primary health care in Denmark represents 90 of all prescribed defined daily doseDDD of antibiotics and that a growing consumption of antibiotics is running alongside increasing resistance to E coli specifically ESBL-producing E coli Extended Spectrum Beta Lactamase Producing E coli
The main cause of E coli infection at primary care level is a Urinary Tract Infection UTI which is one of the most frequent reasons for consultation in general practice in Denmark Interestingly there is no consensus yet about the most effective diagnostic approach to identify those patients that will benefit from antibiotic therapy
Currently in Denmark a wide variety of diagnostic approaches can be identified in primary care settings ie only history taking dipsticks microscopy culture and susceptibility testing in practice Nonetheless there is not conclusive evidence yet about the diagnostic validity of all these approaches and the association with appropriate prescription of antibioticsie correct decision to prescribe and correct choice of antibiotics reflecting the bacterial cause and resistance and impact on patients clinical and microbiological cure
For example some studies that only include uncomplicated UTIs have shown that symptoms alone have a very low predictive value leading to overuse of antibiotics23 However Richards et al after comparing the response to antibiotics of women with symptoms of UTI and a negative dipstick test result concluded that empirical antibiotic use guided only by symptoms was a reasonable option4
Furthermore microscopy and more recent diagnostic tools such as a culture performed in primary care settings have not been included in the latest pragmatic validation studies56 Phase-contrast microscopy is widely used in primary care in Denmark although the very few studies on the subject show wide variation in sensitivity 60-100 and specificity 49-100 of urine microscopy to predict significant bacteriuria
Besides susceptibility testing at primary care level is only done in Denmark and the quality control of the performance of these tests differs across the country MIKAP the Danish agency in charge of the surveillance of the quality of the microbiological tests performed in general practices supervises only some Danish Regions and has not authority on the quality control of the tests carried out in the capital region
In order to curb the development of resistance bacteria strains in patients with urinary tract symptoms and infections we need to increase our knowledge of the validity of the different diagnostic approaches and its impact on proper use of antibiotics and recovery across the heterogeneous group of patients seeking health care in primary care
Objectives
The central research question will be answered throughout the following specific objectives
1 To assess the diagnostic validity ie sensitivity and specificity positive and negative predictive value of different diagnostic approaches in ruling in or ruling out a UTI in different sub-population groups in general practice
2 To describe the impact of different diagnostic approaches on the appropriateness of antibiotic therapy ie decision to prescribe and choice of antibiotic
3 To describe the impact of different diagnostic approaches on clinical and microbiological cure
4 To measure the prevalence of ESBL-resistant Ecoli in patients with urinary tract symptoms in general practice
Materials and Methods
Design and setting Prospective observational study with comparison of different diagnostic approaches to gold standard in general practice
Data Collection Before the index consultation the participating GPs will be asked to complete a background questionnaire about experience organization of the service and access to different diagnostic tools
The day of the index consultation when the GP types the ICPC code for dysuria U01 or frequency U02 as a main motive of consultation a pop-up will automatically appear with a questionnaire about the anamnesis diagnostic approach treatment and other relevant decisions made during the consultation this questionnaire will be directly linked to DAK-EDAMD database Danish General Practice database aimed at improving quality in the delivery of primary medical care services Afterwards the patient will also be asked to provide a urine sample which will be sent to the Statens Serum Institute SSI for culture which will be used as the reference gold standard
The following 14 days after the index consultation the patients will complete a symptom diary attached They will be asked to rate some symptoms each day until recovery or for 7 days if symptoms are ongoing on a 3 point scale from nothing to a lot After 14 days patients will have to send a control urine sample Patients with a persistently positive culture will be followed up after 1and 3 months
Further information about patient background regarding co-morbidities previous hospitalizations and previous use of antibiotics will be gathered from national registers such as The Danish national patients register and The Danish national prescription register
Biobank 10 µl of urine will be stored following the safety and hygiene procedures of the Statens Serum Institute microbiological laboratory only for those urine samples positive for ESBL-producing E coli After detection of a positive resistant strain the samples will be anonymized and stored for a period of 2 years after completion of the current study We plan to carry out further microbiological analysis of the resistant bacteria in collaboration with experts in proteonomics and genomics within the bigger UC-CARE projects The collection of the urine sample does not represent any risk for the patients as it follows the normal procedure in general practice it means the patients is requested to collect a random urine sample in a plastic cup at the practice facility and 14 days after at home
Data management All data will be entered into a database which will be linked to different national registers to obtain detailed data about background information at patient level Data will be screened for data entry errors and extreme values using tables plots and specific commands of the SAS 903
Variables considering the multidimensional and multivariable models that will have to be constructed in order to accurately answer the objectives the following variables with the corresponding data source will be included
Patient level
Patients demographics gender age dysuria frequency supra-pubic pressure polyuria Fever 38oC trembling urine offensive smell gynecological complaints vaginal discharge pruritus low back pain blood in urine Number of days since first symptom started Diagnostic test diagnose treatment severity of symptoms bothersomeness impact on daily activities Previous hospitalization within the last year diagnosis discharge date Consumption of antibiotics within the last year
GP level Number of consultations during office hours due to dysuria andor frequency as a main motive of consultation GPs demographics number of patients in the GPs list point-of-care test for urine examination type of point-of-care tests available in the practice brand and technical specifications for each test Attendance to courses about performance of the tests
Statistical analysis Data will be analyzed using SAS 903 A comparison of proportions will be performed using the chi-square test For the first two objectives the result of the urine culture will be used as the gold standard a cut-off value of 103cfuml or pure growth of Ecoli and 10 4 for more unusual organisms or mixed growth will be used to define a positive cultureand we will calculate sensitivity specificity negative predictive value and positive predictive value for each diagnostic approach against the gold standard
Regarding the third objective prescription of antibiotics and choice of the right antibiotic will be operationalized as binary dependent variables in a logistic regression model while for the last two objectives number of days until symptomatic and microbiological cure will be analyzed as continuous dependent variables in a multiple linear regression model Depending on the number of cases included in the one month and three months follow-up of microbiological cure a Poisson regression model will be developed
The propensity score matching technic will be employed to adjust for pre-test imbalances in the different groups of treatment approaches in order to produce unbiased estimates of the tests effect on the main outcomes and create participant characteristic balance among the groups
Sample calculation Different samples sizes will be needed to compare proper use of antibiotics between the 16 diagnostic profiles Due to the observational design of the study we do not know yet with certainty the distribution of the diagnostic profiles so at least there are two samples sized we are aiming at The first one aims to see a clinically relevant 10 difference in proper use of antibiotics when comparing the diagnostic profiles that affect the decision during the consultation versus the diagnostic profiles that affect the decision after the consultation
The assumptions are a the 4 diagnostic profiles that influence the decision during the consultation are use in 60 of the patients b the correct decision is taken in 60 of the patients in this group while c the correct decision during the consultation is taken only in 40 of the patients in which any of the remaining 12 diagnostic profiles are performed We will need 60 practices recruiting 15 patients each n900 Intra-class correlation 02 α005 and β02
The second sample size relates to the detection of a prevalence of ESBL-producing E Coli between 0 to 6 in patients with a suspected UTI in primary care Our assumptions for the sample calculation are as follows a 60 of patients with symptoms do not have a positive culture b 80 of the patients with a positive culture are infected with a EColi strain Therefore we need 1500 patients with a suspected UTI attending primary care to detect a prevalence of ESBL-resistant Ecoli between 0 to 6 with a 95 confidence interval
Ethics
The study does not represent any risk for the patients due to the observational design It means the diagnostic process and the treatment will be register as it is done in every day practice Participation in the study implies for the patient that they have to fill in a diary about symptoms for 7 days and they should be willing to be contacted 3 days and 14 days after by the personnel from the practice to know whether they have filled in the diary sent it to the research unit and sent the second sample to the microbiological department Consequently the course of the symptomsdisease is not affected by the fact of participating or not in the study
All the personnel at each practice will be informed about the study so as soon as the patient contacts the practice due to the symptoms listed at the inclusion criteria section they will receive the first information about the study
The first contact person ie secretary nurse general practitioner will ask the patient whether they are interested in participating in a project that aims to improve the management of patients with a suspected urinary tract infection If the person is interested in participating in the study then heshe will be given a leaflet with information about the study This leaflet can be read while waiting for the consultation
If the patient has further questions they will be answered during the consultation to guarantee privacy The patient is welcome to have a companion in case they consider it is necessary in order to make a well-informed and thorough decision However due to the fact that these symptoms are acute and non-life-threatening complaints in every day practice the patient uses to come alone It means to guarantee that the patient makes a non-influenced decision the personnel is instructed to emphasize to the patients that they have as much time as the want to think about they can ask questions and they can be sure that they refusal to participating in the project wont change the normal diagnostic process and treatment
The latest report from the Staten Serum Institute SSI1 showed that primary health care in Denmark represents 90 of all prescribed defined daily doseDDD of antibiotics and that a growing consumption of antibiotics is running alongside increasing resistance to E coli specifically ESBL-producing E coli Extended Spectrum Beta Lactamase Producing E coli
The main cause of E coli infection at primary care level is a Urinary Tract Infection UTI which is one of the most frequent reasons for consultation in general practice in Denmark Interestingly there is no consensus yet about the most effective diagnostic approach to identify those patients that will benefit from antibiotic therapy
Currently in Denmark a wide variety of diagnostic approaches can be identified in primary care settings ie only history taking dipsticks microscopy culture and susceptibility testing in practice Nonetheless there is not conclusive evidence yet about the diagnostic validity of all these approaches and the association with appropriate prescription of antibioticsie correct decision to prescribe and correct choice of antibiotics reflecting the bacterial cause and resistance and impact on patients clinical and microbiological cure
For example some studies that only include uncomplicated UTIs have shown that symptoms alone have a very low predictive value leading to overuse of antibiotics23 However Richards et al after comparing the response to antibiotics of women with symptoms of UTI and a negative dipstick test result concluded that empirical antibiotic use guided only by symptoms was a reasonable option4
Furthermore microscopy and more recent diagnostic tools such as a culture performed in primary care settings have not been included in the latest pragmatic validation studies56 Phase-contrast microscopy is widely used in primary care in Denmark although the very few studies on the subject show wide variation in sensitivity 60-100 and specificity 49-100 of urine microscopy to predict significant bacteriuria
Besides susceptibility testing at primary care level is only done in Denmark and the quality control of the performance of these tests differs across the country MIKAP the Danish agency in charge of the surveillance of the quality of the microbiological tests performed in general practices supervises only some Danish Regions and has not authority on the quality control of the tests carried out in the capital region
In order to curb the development of resistance bacteria strains in patients with urinary tract symptoms and infections we need to increase our knowledge of the validity of the different diagnostic approaches and its impact on proper use of antibiotics and recovery across the heterogeneous group of patients seeking health care in primary care
Objectives
The central research question will be answered throughout the following specific objectives
1 To assess the diagnostic validity ie sensitivity and specificity positive and negative predictive value of different diagnostic approaches in ruling in or ruling out a UTI in different sub-population groups in general practice
2 To describe the impact of different diagnostic approaches on the appropriateness of antibiotic therapy ie decision to prescribe and choice of antibiotic
3 To describe the impact of different diagnostic approaches on clinical and microbiological cure
4 To measure the prevalence of ESBL-resistant Ecoli in patients with urinary tract symptoms in general practice
Materials and Methods
Design and setting Prospective observational study with comparison of different diagnostic approaches to gold standard in general practice
Data Collection Before the index consultation the participating GPs will be asked to complete a background questionnaire about experience organization of the service and access to different diagnostic tools
The day of the index consultation when the GP types the ICPC code for dysuria U01 or frequency U02 as a main motive of consultation a pop-up will automatically appear with a questionnaire about the anamnesis diagnostic approach treatment and other relevant decisions made during the consultation this questionnaire will be directly linked to DAK-EDAMD database Danish General Practice database aimed at improving quality in the delivery of primary medical care services Afterwards the patient will also be asked to provide a urine sample which will be sent to the Statens Serum Institute SSI for culture which will be used as the reference gold standard
The following 14 days after the index consultation the patients will complete a symptom diary attached They will be asked to rate some symptoms each day until recovery or for 7 days if symptoms are ongoing on a 3 point scale from nothing to a lot After 14 days patients will have to send a control urine sample Patients with a persistently positive culture will be followed up after 1and 3 months
Further information about patient background regarding co-morbidities previous hospitalizations and previous use of antibiotics will be gathered from national registers such as The Danish national patients register and The Danish national prescription register
Biobank 10 µl of urine will be stored following the safety and hygiene procedures of the Statens Serum Institute microbiological laboratory only for those urine samples positive for ESBL-producing E coli After detection of a positive resistant strain the samples will be anonymized and stored for a period of 2 years after completion of the current study We plan to carry out further microbiological analysis of the resistant bacteria in collaboration with experts in proteonomics and genomics within the bigger UC-CARE projects The collection of the urine sample does not represent any risk for the patients as it follows the normal procedure in general practice it means the patients is requested to collect a random urine sample in a plastic cup at the practice facility and 14 days after at home
Data management All data will be entered into a database which will be linked to different national registers to obtain detailed data about background information at patient level Data will be screened for data entry errors and extreme values using tables plots and specific commands of the SAS 903
Variables considering the multidimensional and multivariable models that will have to be constructed in order to accurately answer the objectives the following variables with the corresponding data source will be included
Patient level
Patients demographics gender age dysuria frequency supra-pubic pressure polyuria Fever 38oC trembling urine offensive smell gynecological complaints vaginal discharge pruritus low back pain blood in urine Number of days since first symptom started Diagnostic test diagnose treatment severity of symptoms bothersomeness impact on daily activities Previous hospitalization within the last year diagnosis discharge date Consumption of antibiotics within the last year
GP level Number of consultations during office hours due to dysuria andor frequency as a main motive of consultation GPs demographics number of patients in the GPs list point-of-care test for urine examination type of point-of-care tests available in the practice brand and technical specifications for each test Attendance to courses about performance of the tests
Statistical analysis Data will be analyzed using SAS 903 A comparison of proportions will be performed using the chi-square test For the first two objectives the result of the urine culture will be used as the gold standard a cut-off value of 103cfuml or pure growth of Ecoli and 10 4 for more unusual organisms or mixed growth will be used to define a positive cultureand we will calculate sensitivity specificity negative predictive value and positive predictive value for each diagnostic approach against the gold standard
Regarding the third objective prescription of antibiotics and choice of the right antibiotic will be operationalized as binary dependent variables in a logistic regression model while for the last two objectives number of days until symptomatic and microbiological cure will be analyzed as continuous dependent variables in a multiple linear regression model Depending on the number of cases included in the one month and three months follow-up of microbiological cure a Poisson regression model will be developed
The propensity score matching technic will be employed to adjust for pre-test imbalances in the different groups of treatment approaches in order to produce unbiased estimates of the tests effect on the main outcomes and create participant characteristic balance among the groups
Sample calculation Different samples sizes will be needed to compare proper use of antibiotics between the 16 diagnostic profiles Due to the observational design of the study we do not know yet with certainty the distribution of the diagnostic profiles so at least there are two samples sized we are aiming at The first one aims to see a clinically relevant 10 difference in proper use of antibiotics when comparing the diagnostic profiles that affect the decision during the consultation versus the diagnostic profiles that affect the decision after the consultation
The assumptions are a the 4 diagnostic profiles that influence the decision during the consultation are use in 60 of the patients b the correct decision is taken in 60 of the patients in this group while c the correct decision during the consultation is taken only in 40 of the patients in which any of the remaining 12 diagnostic profiles are performed We will need 60 practices recruiting 15 patients each n900 Intra-class correlation 02 α005 and β02
The second sample size relates to the detection of a prevalence of ESBL-producing E Coli between 0 to 6 in patients with a suspected UTI in primary care Our assumptions for the sample calculation are as follows a 60 of patients with symptoms do not have a positive culture b 80 of the patients with a positive culture are infected with a EColi strain Therefore we need 1500 patients with a suspected UTI attending primary care to detect a prevalence of ESBL-resistant Ecoli between 0 to 6 with a 95 confidence interval
Ethics
The study does not represent any risk for the patients due to the observational design It means the diagnostic process and the treatment will be register as it is done in every day practice Participation in the study implies for the patient that they have to fill in a diary about symptoms for 7 days and they should be willing to be contacted 3 days and 14 days after by the personnel from the practice to know whether they have filled in the diary sent it to the research unit and sent the second sample to the microbiological department Consequently the course of the symptomsdisease is not affected by the fact of participating or not in the study
All the personnel at each practice will be informed about the study so as soon as the patient contacts the practice due to the symptoms listed at the inclusion criteria section they will receive the first information about the study
The first contact person ie secretary nurse general practitioner will ask the patient whether they are interested in participating in a project that aims to improve the management of patients with a suspected urinary tract infection If the person is interested in participating in the study then heshe will be given a leaflet with information about the study This leaflet can be read while waiting for the consultation
If the patient has further questions they will be answered during the consultation to guarantee privacy The patient is welcome to have a companion in case they consider it is necessary in order to make a well-informed and thorough decision However due to the fact that these symptoms are acute and non-life-threatening complaints in every day practice the patient uses to come alone It means to guarantee that the patient makes a non-influenced decision the personnel is instructed to emphasize to the patients that they have as much time as the want to think about they can ask questions and they can be sure that they refusal to participating in the project wont change the normal diagnostic process and treatment
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