Infectious Diseases Experts as Part of the Antibiotic Stewardship Team in Primary Care

Infectious Diseases Experts as Part of the Antibiotic Stewardship Team in Primary Care: A Cluster-randomized Blinded Study (IDASP)

Sponsors

Lead Sponsor: Institut d'Investigació Biomèdica de Bellvitge

Source Institut d'Investigació Biomèdica de Bellvitge
Brief Summary

A cluster-randomised muticentre blinded clinical trial will be performed in six primary care centres located in the southern metropolitan area of Barcelona (Spain). The objective is to assess whether including experts on infectious diseases (ID) within the antimicrobial stewardship (AMS) team of primary care achieves higher reductions on overall antibiotic consumption and increases the quality of prescription in diagnosed upper respiratory and urinary tract infections. Centres will be randomly assigned to receive a standard-AMS or an advanced-AMS (intervention). Advanced-AMS includes all standard-AMS strategies plus general practitioner chance to discuss clinical cases by telephone to ID expert on working days (8:00 am to 8:00 pm), and by biweekly meetings.

Detailed Description

STUDY DESIGN. A cluster-randomised, multicentre blinded clinical trial will be conducted in six primary care centres between June 2021 and June 2023. SCOPE OF STUDY. Six primary care centres in the southern metropolitan area of Barcelona. SUBJECTS OF STUDY. General practitioners of the participating centres. Paediatricians are excluded. Patients older than 14 years who have a diagnosis of upper respiratory tract or urinary tract infections will be prospectively follow up to assess information related to secondary outcomes. Each patient could be included more than once if the GP visit is 30 days or more apart from the initial medical assessment. Eligible patients will be identified following the International Classification of Diseases ICD-10 CM codes as follows: Upper respiratory tract infection: J00, J01, J01.0, J01.1, J01.2, J01.3, J01.4, J01.8, J01.9, J02, J02.0, J02.8, J01.9, B30.2, J03, J03.00, J03.01, J03.80, J03.81, J03.9, J03.91, J04, J04.0, J04.1, J04.2, J05, J05.0, J05.1, J06, J06.0, J06.9. Urinary tract infection: N10, N30.0, N30.1, N30.2, N30.3, N30.4, N30.8, N30.9, N39.0. TIMELINE. From June to September standard-AMS will be promoted to increase understanding and acceptance of AMS by general practitioners. Baseline data collection will begin on October 2021 and will last six months. After these six months, centres will be randomly assigned to receive an advanced-AMS (intervention group) or to continue the standard-AMS (control group). The intervention will be spanned 12 months (31 March 2023). RANDOMIZATION. A centralised electronic computer system will generate a random list based on permuted blocks. To ensure similar characteristics among centres permuted blocks will be created with stratification on the total number of referral population and the number of population older than 65 years old by centre. Investigators will be unaware of the block size and the permutation procedure. The 6 centers will be arranged into two groups: 3 on the control group and 3 in the intervention group. STUDY GROUPS. Centres will be assigned to receive an advanced-AMS (intervention group) or a standard-AMS (control group). The control group will have an standard antibiotic optimization program that will consist on: 1. Informative flyers addressed to patients to increase awareness about antibiotic indications and potential harms of its misuse. 2. Updated local antibiotic guidelines for treating common infections according to local resistance patterns. 3. Promotion of delayed antibiotic prescription. 4. Promotion of Streptococcal pyogenes antigen test (Streptotest) if bacterial tonsillitis is suspected. 5. Daily microbiological report of resistant bacteria isolates to general practitioners. 6. Annual reports to prescribers of main AMS outcomes at centre-level. The intervention group will have the same standard-AMS program enhanced with: - Telephone access to ID expert on working days (8:00 am to 8:00 pm). - Biweekly meetings among GP and infectious diseases experts to discuss clinical cases. BLINDING. Two secondary end-points (unnecessary antibiotic therapy and adequacy of therapy), will be evaluated by two independent investigators who will be blinded to centre allocation. Discrepant decisions among them will be discussed with a third blinded physician to achieve consensus. The degree of agreement will be recorded with the kappa statistic analysis. The centre allocation will not be blinded for the participating centres and general practitioners. OUTCOMES. Outcomes will be measured in each primary center with a mensual periodicity during 12 consecutive months. These variables are: - Main objective. To assess the impact of advanced-AMS on overall antibiotic consumption measured by defined daily dose of antibiotic per 1.000 inhabitats per day (DHD). - Secondary objectives: - To assess the impact of the advanced-AMS on unnecessary antibiotic prescriptions in diagnosed upper respiratory and urinary tract infections. - To evaluate the impact of the advanced-AMS on the adequacy of antibiotic prescriptions. - To evaluate the impact of the advanced-AMS on the total number of re-attendance to general practitioners or emergency department for any reason within 30 days after the initial GP evaluation. - To evaluate the impact of the advanced-AMS on the number of hospital admissions for any reason within 30 days after the initial GP visit. DEFINITIONS. - DHD are calculated by the following the World Health Organisation criteria (https://www.who.int/tools/atc-ddd-toolkit/indicators). - Unnecessary prescription will be considered as follows: - An antibiotic prescribed in upper respiratory infections, which is in disagreement with the local antibiotic guidelines. - An antibiotic is prescribed in asymptomatic bacteriuria, which is defined as having a positive urine culture with ≥ 10EXP5 CFU/ml of an uropathogen in patients without signs or symptoms of urinary tract infection (dysuria, urinary frequency or urgency, suprapubic pain, fevers, or flank pain). Pregnant women and patients undergoing urologic interventions are excluded from this definition. - Adequacy of antibiotic therapy will be considered when prescription fulfils the local guidelines: type of antibiotic + dose, and length of therapy. DATA COLLECTION AND MONITORING. Monthly DHD will be calculated based on the dispensing data of our electronic prescribing system of the Catalan Institute of Health. To get information regarding secondary outcomes, patients who fulfil ICD-10 CM codes on the last working day of every month will be selected by a cross-sectional analysis. On these selected patients, information from electronic medical records (SAP logon® and eCAP) will be obtained. Investigator will obtain the following variables: demographics, Charlson score, type of infection, antibiotic prescribed, doses and length of antibiotic therapy, re-attendance to the general practitioner, attendance to the emergency department, and hospital admission. All the included patients will be followed up 30 days after the initial primary care physician visit. To ensure completeness of data, a telephone call will be allowed if any crucial data is missing in the electronic medical record. Information regarding the burden of the intervention such as the number of telephone calls received by the ID expert per month and the number of participants to biweekly meetings with the ID will be also collected. All data will be recorded by the study monitor on a standardized data abstraction form by using RedCap (Research Electronic Data Capture) hosted at IDIBELL, a secure web application for building and managing online databases. SAMPLE SIZE. The intervention area has a total of 20 primary care centers and a reference population of 286,278 inhabitants. Six centers will be included, three in each study arm, implying an approximate coverage of 35% of the referral population (100,200 inhabitants). The consumption of antibiotics in 2017 was 8.94 DHD, and it's expected to reduce this consumption by 10% in the intervention group. The number of 3 clusters per arm will allow rejecting the null hypothesis of equal consumption with a power of 80%, assuming a moderate intra-cluster correlation of 0.2, an intra-cluster variance of 4, and a mean difference of 1 DHD. Type I error is set at 5%. STATISTICAL ANALYSIS. A descriptive analysis will be performed on the monthly consumption of antibiotics expressed in DHD by the study group (control and intervention), period, and cluster. The monthly consumption of antibiotics evolution will be represented on a graph by months, and a smoothed curve will be estimated using locally weighted smoothing (LOESS). Antibiotic consumptions will be compared according to the study group using a time series model. Where the dependent variable will be the monthly consumption of antibiotics expressed in DHDs and the independent variable will be the study group. In the estimation of the model, the seasonality, the trend, and the first and second-order lags of the series will be analyzed. Also, the use of hierarchical models due to cluster design will be taken into account. A descriptive analysis of the demographic and clinical profile of the patients surveyed will be performed. A McNemar test will be used to compare, between the study groups, the percentage of patients with an unnecessary prescription for the upper respiratory and urinary tract, the percentage of patients with an adequate prescription according to the guidelines, the percentage of patients who revisit general practitioner or emergency room at 30 days, and the percentage of patients with hospital admission at 30 days. Also, log-binomial regression models will be performed, to estimate the effect of the intervention in terms of risk on the above-mentioned outcomes adjusting by patients' clinical profile. To estimate models it will be accounted that patients are nested in primary care clusters, so a correction of the standard errors is carried out through the variance-covariance matrix. Data management and statistical analysis will be carried out with the statistical package R version 4.0.1 or higher. LIMITATIONS. The study does not contemplate randomization by prescribing physician but by conglomerates to avoid possible contamination effects at the prescribing physician and patients in the same center. As it is a cluster analysis, there could be differences in the degree of prescription of doctors within the same center and between the different centers. In order to reduce this problem, the variability of prescribing intra-cluster and between clusters has been calculated during the period 2017 in a group of primary care centers in the intervention area, differences that have been taken into account for the calculation of the sample. Design of the present study does not include a third group without any AMS intervention due to department policies during 2019. However, to achieve the best result interpretation, an historic of the antibiotic consumption in the participating centers will act as a control group, and a baseline period with only an standard-AMS intervention will be performed. Comparisons between all stages of the clinical trial will be performed to obtain more robust data. ETHICAL ASPECTS. This research will be carried out under the standards of good clinical practices following the principles of the Declaration of Helsinki (Fortaleza, 2013), as well as the current legislation applicable to this type of study. This study has been approved by the Ethics Committee of Hospital Universitari de Bellvitge and the Foundation University Institute for Primary Health Care Research Jordi Gol i Gurina (IDIAPJGol) who waived the need to obtain informed consent since the intervention is mainly aimed at health-care professionals (general practitioners) who will be previously informed of the objective and other relevant aspects of the study (REF. PR277/19 - REF. 4R20/26). Clinical data treatment of the included patients in the research project as well as that of associated professionals (primary care physicians) will be carried out following the established by the Organic Law 3/2018, of December 5, and by Regulation (EU) 2016/679 of the European Parliament and of the Council of April 27, 2016 on Data Protection (RGPD). Based on these regulations, the sponsor will guarantee the protection of the confidentiality of the participants in the program, both patients and doctors. The data collection sheets will be identified with a code. The name of the doctor or patient will not appear in any document, or any publication or communication of the study results.

Overall Status Not yet recruiting
Start Date 2021-06-01
Completion Date 2024-06-30
Primary Completion Date 2023-03-31
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
To asses the impact of implementing an advanced-AMS program (iclusion of infectious diseases especialists) on the overal antibiotic consumption. Through study completion, an average of 1 year and a half
Secondary Outcome
Measure Time Frame
Number of patients with unnecessary antibiotic prescriptions on high respiratory pathway infections. Through study completion, an average of 1 year and a half
Number of patients with unnecessary antibiotic prescriptions on urinary tract infections. Through study completion, an average of 1 year and a half
Number of patients with an adequate antibiotic treatment Through study completion, an average of 1 year and a half
Number of patients re-consulting after completing antibiotic therapy. Through study completion, an average of 1 year and a half
Numer of cases who needs hospitalitzation 30 days after antibiotic therapy. Through study completion, an average of 1 year and a half
Enrollment 160000
Condition
Intervention

Intervention Type: Behavioral

Intervention Name: Advanced AMS program

Description: - Telephone acces to infectious disease experts to discuss patients' therpies during working days. - Biweeckly meetings with infectious diseases experts and antimicrobial stewardship group.

Arm Group Label: Advanced AMS program

Eligibility

Criteria:

All general practitioners of the 6 primary care centers will be included in our clinical trial, excepting paediatricians. Data collection will be performed on patients attended in these centres. Inclusion and exclusion criteria will be applied on the patients attended by general practitioners: Inclusion criteria: - Patients older than 14 years old diagnosed with respiratory infections. - Patients older than 14 years old diagnosed with urinary tract infections. Exclusion criteria: - Patients less than 14 years old.

Gender:

All

Minimum Age:

14 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Overall Contact

Last Name: Ariadna A Padullés-Zamora, PhD

Phone: +34 96 260 75 04

Email: [email protected]

Verification Date

2021-04-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Institut d'Investigació Biomèdica de Bellvitge

Investigator Full Name: Ariadna Padullés Zamora

Investigator Title: Principal Investigator

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Advanced AMS program

Type: Experimental

Description: Conglomerate of three randomily assigned primary care centers in which an infectious diseases expert will be continuously in touch with primary care practitioners to solve all doubts about urinary and respiratory tract infections; and will have a biweeckly reunion with an infectious diseases comitee.

Label: Standard AMS program

Type: No Intervention

Description: Conglomerate of three primary care centers in which a typical AMS will be promoted. This will include: Informative flyers addressed to patients to increase awareness about antibiotic indications and potential harms of its misuse. Updated the local antibiotic guidelines for treating common infections according to local resistance patterns. Promotion of delayed antibiotic prescription. Promotion of Streptococcal pyogenes antigen test (Streptotest) if bacterial tonsillitis is suspected. Daily microbiological report of resistant bacteria isolates to general practitioners. Trimestral reports to prescribers of main AMS outcomes at centre-level.

Acronym IDASP
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Six primary care centers will be randomized by conglomerates in 3 parallel groups. First group with three randomized centers will receive a conventional AMS (control group), meanwhile the three other parallel randomized centers will include an infectious diseases specialist in the ASM group to discuse all cases by telephone, and a biweeckly meeting (interventional group). List of study sites: El Castells from Castelldefels, Prat de Llobregat 2, Gava 1, Viladecans 2, Hospitalet de Llobregat 2 Sant Josep and Santa Eulàlia Nord.

Primary Purpose: Health Services Research

Masking: Single (Outcomes Assessor)

Masking Description: Evaluators of secondary outcomes will be blind related to the intervention.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News