Clinical trial NCT04001309: Antimicrobial Stewardship Interventions in a Hospital Setting
Official title: A Randomized Antimicrobial Stewardship Trial in a Hospital Setting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infectious Disease
Keywords: antimicrobial stewardship
prospective audit and feedback
infectious diseases
randomized trial
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Lund University
First posted: 2019-06-28
Enrollment: 1312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized clinical trial
Primary purpose: TREATMENT

Brief summary: The emerging crisis of multidrug-resistant bacteria is accelerated by a massive overuse and misuse of antibiotics. It has been estimated that 50% of antibiotic prescriptions are inappropriate. Antibiotic interventions to improve prescribing patterns have been successfully implemented in primary care in Sweden and other countries. However, much of the last-resort antibiotics are used in hospitals in which decisions on therapy for bacterial infections are more complex. In this project we will explore the appropriateness of antibiotic prescribing in a hospital setting and measures to improve the quality of antimicrobial therapy. Antimicrobial stewardship interventions will be conducted at selected hospital departments using prospective audit and feedback in a multifaceted and cross-disciplinary approach. The intervention effects on antibiotic consumption, appropriateness of prescriptions, patient outcome and emergence of resistance will be evaluated, and a financial cost-effectiveness analysis will be performed.

Detailed description: Background: In this project we will address the issue of inappropriate antibiotic prescribing in a hospital setting using a systematic and cross-disciplinary approach. We believe that a substantial reduction in antibiotic use and a significant improvement in prescribing patterns can be achieved, which will benefit the patients by reducing the risks of side effects such as antibiotic-induced Clostridium difficile enteritis.

Aim: The aim of this study is to implement and evaluate antibiotic interventions at targeted hospital wards.

Method: Hospital wards will be randomised to one of two antimicrobial stewardship intervention arms stratified by specialty (medicine or surgery). Prospective audit and feedback is a core intervention strategy in both arms.

Statistics: Interrupted time-series analysis (ITS) will be used for the primary endpoint; volume of antimicrobial prescribing. Monthly baseline data at least five years prior to start of the intervention and a during a follow-up period of at least 12 months after end of the intervention period will be used to assess immediate and sustained effects.

Endpoints and outcomes:

* Primary endpoint is reduction in antibiotic use, days of antibiotic therapy (DOTs)/100 patient days
* Secondary endpoints include outcome measures for quantity of antibiotic use, appropriateness of prescriptions, clinical and microbiological outcome and cost-effectiveness.

Data on antibiotic use and trends in prescriptions of key antibiotics will be obtained from hospital pharmacies. Data on duration of hospitalization, patient mortality, re-admissions and side effects including antibiotic-associated Clostridium difficile enteritis will be extracted from the medical records to assess potential impact on patient outcome caused by the intervention. Data on emergence of resistance during therapy and general trends in resistance epidemiology will be recorded. The outcome assessment will include a survey to participating physicians on the value different aspects of the stewardship intervention in their daily care of patients with infections. A cost-effectiveness analysis of the intervention will be performed.

Eligibility criteria: Randomization to intervention arms is performed on ward level.

Eligibility criteria:

- Surgical or medical wards

Patient level (too be included in the outcome analyses)

Inclusion Criteria:

* At least 18 years of age
* Ongoing antimicrobial therapy on a study ward
* Signed informed consent

Exclusion Criteria:

* Patients in palliative care with very short life expectancy
* Patients from another county than study site

Primary outcomes:
measure: Change and trends in days of antibiotic therapy (DOT)/100 patient days
timeFrame: 7 years
Secondary outcomes:
measure: Days of defined daily doses (DDDs)/100 patient days
timeFrame: 12 months
measure: Treatment duration (Days per treatment period overall)
timeFrame: 12 months
measure: 30-d mortality
timeFrame: 12 months
measure: In-hospital mortality
timeFrame: 12 months
measure: Hospital readmission within 30 d after discharge
timeFrame: 12 months
measure: Hospital readmission due to relapse of infection within 30 d after discharge
timeFrame: 12 months
measure: Hospital length of stay (LOS)
timeFrame: 12 months
measure: Intensive Care Unit (ICU) transfer
timeFrame: 12 months
measure: Guideline compliance
timeFrame: 12 months
measure: De-escalation or shift to targeted therapy
timeFrame: 12 months
measure: Intravenous to oral switch
timeFrame: 12 months
measure: Appropriate diagnostic examinations
timeFrame: 12 months
measure: Dose adjustment for renal function within 48 h after initiation of antimicrobial therapy at admission
timeFrame: 12 months
measure: Dose adjustment for renal function when initiating antimicrobial therapy in a non-acute situation
timeFrame: 12 months
measure: Therapeutic drug monitoring (TDM)
timeFrame: 12 months
measure: Drug-drug interactions (DDI)
timeFrame: 12 months
measure: Incidence of Clostridium difficile infections (CDI)
timeFrame: 12 months
measure: Incidence of multidrug-resistant organisms (MDRO)
timeFrame: 12 months
measure: Costs of administered antimicrobials
timeFrame: 12 months
measure: Costs of the intervention
timeFrame: 12 months
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Ystad
country: Sweden
facility: Ystads lasarett
Study officials:
affiliation: Uppsala University Hospital
name: Thomas Tängdén, MD, Phd
role: PRINCIPAL_INVESTIGATOR
References: