The trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias: study protocol for a cluster randomized controlled trial

Abstract

Background: Infections are common in nursing home (NH) residents with advanced dementia but are often managed inappropriately. Antimicrobials are extensively prescribed, but frequently with insufficient evidence to support a bacterial infection, promoting the emergence of multidrug-resistant organisms. Moreover, the benefits of antimicrobials remain unclear in these seriously ill residents for whom comfort is often the goal of care. Prior NH infection management interventions evaluated in randomized clinical trials (RCTs) did not consider patient preferences and lack evidence to support their effectiveness in 'real-world' practice.

Methods: This report presents the rationale and methodology of TRAIN-AD (Trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias), a parallel group, cluster RCT evaluating a multicomponent intervention to improve infection management for suspected urinary tract infections (UTIs) and lower respiratory tract infections (LRIs) among NH residents with advanced dementia. TRAIN-AD is being conducted in 28 facilities in the Boston, USA, area randomized in waves using minimization to achieve a balance on key characteristics (N = 14 facilities/arm). The involvement of the facilities includes a 3-month start-up period and a 24-month implementation/data collection phase. Residents are enrolled during the first 12 months of the 24-month implementation period and followed for up to 12 months. Individual consent is waived, thus almost all eligible residents are enrolled (target sample size, N = 410). The intervention integrates infectious disease and palliative care principles and includes provider training delivered through multiple modalities (in-person seminar, online course, management algorithms, and prescribing feedback) and an information booklet for families. Control facilities employ usual care. The primary outcome, abstracted from the residents' charts, is the number of antimicrobial courses prescribed for UTIs and LRIs per person-year alive.

Discussion: TRAIN-AD is the first cluster RCT testing a multicomponent intervention to improve infection management in NH residents with advanced dementia. Its findings will provide an evidence base to support the benefit of a program addressing the critical clinical and public health problem of antimicrobial misuse in these seriously ill residents. Moreover, its hybrid efficacy-effectiveness design will inform the future conduct of cluster RCTs evaluating nonpharmacological interventions in the complex NH setting in a way that is both internally valid and adaptable to the 'real-world'.

Trial registration: ClinicalTrials.gov, NCT03244917 . Registered on 10 August 2017.

Keywords: Antimicrobials; Cluster randomized trial; Decision-making; Dementia; Goals of care; Implementation; Infections; Nursing homes; Palliative care; Pragmatic trial.

Fig. 1

Schedule of enrolment, intervention, and assessments. ^aThe Institutional Review Board waived individual consent and thus almost all eligible residents are enrolled. ^bThe Trial to Reduce Antimicrobial Use in Nursing Home Residents with Alzheimer’s Disease and other Dementias. ^cResident assessments include chart reviews done at baseline (2-month look back), every 2 months and death, and each resident is followed for up to 12 months. ^dBedford Alzheimer Nursing Severity-Subscale (BANS-S: range 7–28, higher scores indicate more functional disability) [32]. ^eUrinary tract (UTIs) and lower respiratory tract (LRIs) infections. ^fVital signs (e.g., temperature, respiratory rate), localized signs and symptoms (e.g., cough, hematuria) are recorded 24 h before or 72 h after initial documentation of the suspected infection. ^gInvestigations include urinalysis and urine, blood cultures, complete blood counts, and chest x-rays. ^hAny new major acute illnesses other than infections such as bone fracture, stroke, or seizures. ⁱFacility data are collected from three sources: LTCfocus.org website [31]; Medicare.gov website (Medicare NH Compare) [33]; and survey administered to a senior administrator. ^jMinimum Data Set Cognitive Function Scale (MDS CFS; score = 4 indicates severe impairment) [34]. ^kNursing Home Compare five-star rating (range 0–5; higher scores indicate better care quality)

Fig. 2

CONSORT diagram of facilities recruitment, randomization, and resident participation as of 25 July 2019. Anticipated completion of resident enrollment is 11 June 2020. Group A and B represent each trial arm, whose identity remains masked

Fig. 3

Study timetable of waves of intervention (I) and control (C) nursing home (NH) recruitment

Fig. 4

Algorithms for managing suspected UTIs and LRIs infections in nursing home residents with advanced dementia. CFU colony-forming units, HR heart rate, LRI lower respiratory tract infection, RR respiratory rate, T temperature, U/A urinalysis, UTI urinary tract infection

Fig. 5

Proportions of targeted providers completing the training seminar (blue circle) and online course (dotted circle). The Venn diagrams display proportions for all providers (a; N = 341), prescribing providers (physicians, nurse practitioners, and physician assistants) (b; N = 74), and nurses (c; N = 267). The numbers correspond to the 13 facilities which have completed the 3-month start-up period as of 31 July 2019 and exclude those from the remaining facility in which providers are currently offered the training seminar and online course