Reducing Antibiotic Use for Dementia

(TRAIN-AD 2 Trial)

Overseen By Susan Mitchell, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Hebrew SeniorLife

Disqualifiers: Age < 60, No dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new approach, called TRAIN AD 2.0, can manage suspected infections in nursing home residents with dementia while reducing antibiotic use. The trial compares this intervention to usual care to identify which method results in less antibiotic usage and fewer uncomfortable procedures. Suitable participants include those with moderate to severe dementia who have lived in a nursing home for over 90 days. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What is the safety track record for TRAIN AD 2.0?

Research shows that people with dementia can sometimes react poorly to medications, but specific safety information for the TRAIN AD 2.0 treatment is not yet available. Since TRAIN AD 2.0 is being tested in a Phase 4 trial, it has already demonstrated safety in earlier stages. Phase 4 trials typically occur after a treatment receives approval for use, indicating it is generally safe and well-tolerated. However, because this study focuses on a new method for managing infections rather than a new drug, the risk of serious side effects might be lower. The trial aims to improve infection management and potentially reduce unnecessary antibiotic use, which could help avoid some medication-related side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about TRAIN AD 2.0 because it takes a fresh approach to managing suspected infections in dementia patients by focusing on improving the decision-making process, rather than just prescribing antibiotics. Unlike the standard practice, which often relies heavily on antibiotics, TRAIN AD 2.0 introduces comprehensive support for healthcare providers through orientation sessions, online courses, and clear guidelines to enhance infection management and communication with patients' families. This method not only aims to reduce unnecessary antibiotic use, which can lead to resistance, but also promises to improve overall care for dementia patients by promoting more thoughtful and informed treatment decisions.

What evidence suggests that the TRAIN AD 2.0 intervention is effective for reducing antibiotic use in dementia patients?

Research has shown that the initial TRAIN-AD program did not significantly reduce antibiotic use in nursing home residents with advanced dementia. The current trial's TRAIN AD 2.0 arm aims to improve on this with a more comprehensive approach. This includes training sessions, online courses, and infection management guidelines for healthcare providers. The goal is to improve infection management, potentially reducing unnecessary antibiotic use. While evidence on its effectiveness is still being gathered, this structured approach is designed to enhance care and reduce unnecessary treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Susan Mitchell, MD, MPH

Principal Investigator

Hebrew SeniorLife

Are You a Good Fit for This Trial?

This trial is for nursing home residents over 60 years old with a diagnosis of any type of dementia, who have lived in the facility for more than 90 days. They must have moderate to severe cognitive impairment. It's not suitable for those without or with only mild cognitive issues.

Inclusion Criteria

NH length of stay >90 days

Cognitive Functional Scale (CFS) > 1

I have been diagnosed with a form of dementia.

Exclusion Criteria

Does not have diagnosis of dementia

Does not meet CFS >1 score

Living in nursing home for less than 90 days

Timeline for a Trial Participant

Preparation

Preparation phase for setting up the trial, including randomization and program roll out at the facility level

8 months

Startup

Initial startup period for the trial in all nursing homes

2 months

Resident Enrollment

Enrollment of eligible residents with dementia using the EHR and Minimum DataSet (MDS)

12 months

Intervention Implementation

Implementation of the multicomponent intervention in the experimental arm nursing homes

24 months

Data Collection

Data collection period for all nursing homes

24 months

Follow-up

Participants are monitored for safety and effectiveness after the intervention

12 months

Data Analysis and Manuscript Preparation

Analysis of collected data and preparation of manuscripts

10 months

What Are the Treatments Tested in This Trial?

Interventions

• TRAIN AD 2.0

Trial Overview The study tests TRAIN AD 2.0, an intervention designed to optimize infection management among dementia patients, aiming to reduce antibiotic use and avoid unnecessary treatments compared to standard care practices.

How Is the Trial Designed?

Group I: TRAIN AD 2.0 Experimental Treatment 1 Intervention

Nursing homes randomized to the experimental arm will emply a multicomponent intervention among their providers designed to improve the management of suspected infections in residents with dementia. The components include: a.Orientation sessions for providers, b.On-line case based course for providers, c.Infection management algorithms for providers, d. Guidelines for providers to communicate with proxies, and e. Education booklet about infections in dementia for providers.

Group II: Usual Care Active Control 1 Intervention

Nursing homes randomized to the conrol arm will employ usual care to manage nursing home residents with dementia with suspected infections.

Who Is Running the Clinical Trial?

Hebrew SeniorLife

Lead Sponsor

Trials

52

Recruited

273,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Published Research Related to This Trial

In a study of 240 elderly patients with advanced dementia, 64% experienced suspected pneumonia episodes in their last six months, highlighting pneumonia as a common terminal condition in this population.

The aggressiveness of antibiotic treatment for pneumonia was influenced by factors such as the presence of a do-not-hospitalize order, aspiration events, the patient's primary language, and unstable vital signs, indicating the importance of advance care planning and clinical assessment in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence and treatment of suspected pneumonia in long-term care residents dying with advanced dementia. Chen, JH., Lamberg, JL., Chen, YC., et al.[2008]

The introduction of the West Wales ADR Profile for Mental Health Medicines significantly increased the number of clinical problems addressed in dementia patients, from an average of 6.02 to 9.86, indicating improved monitoring and care.

Using the ADR Profile led to a reduction in the prescribing of mental health medications, suggesting it can enhance the safety and quality of care for individuals with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial. Jordan, S., Gabe-Walters, ME., Watkins, A., et al.[2018]

This study will evaluate the effectiveness of a clinician champion intervention over 24 months to reduce the use of potentially inappropriate medications (PIMs) in people living with dementia, aiming to improve medication safety.

The trial will also assess whether this intervention leads to fewer emergency department visits and hospitalizations due to falls, using Medicare claims data to track outcomes in two participating accountable care organizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can clinician champions reduce potentially inappropriate medications in people living with dementia? Study protocol for a cluster randomized trial. Parchman, ML., Perloff, J., Ritter, G.[2022]

The prevalence of dementia among veterans aged 65 and older was found to be 4.8% using only Veterans Health Administration (VHA) data, but increased to 7.4% when combined with Medicare data, highlighting the importance of comprehensive data sharing.

The average annual cost attributable to dementia was estimated at $10,950 per veteran using VHA data alone, but this figure dropped to $6,662 when considering combined VHA and Medicare data, suggesting that integrated data can provide a more accurate picture of healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attributable Cost of Dementia: Demonstrating Pitfalls of Ignoring Multiple Health Care System Utilization. Lei, L., Cooley, SG., Phibbs, CS., et al.[2019]

A study of 3,913 E. coli and 1,736 K. pneumoniae urine isolates from home-based primary care patients with dementia revealed high annual rates of antimicrobial resistance between 2014 and 2018, with ciprofloxacin resistance at 18%-23% for E. coli and 5%-7% for K. pneumoniae.

Multidrug resistance was also significant, affecting 9%-11% of E. coli and 5%-6% of K. pneumoniae isolates, indicating a need for further research on antimicrobial resistance in home-care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial resistance in Escherichia coli and Klebsiella pneumoniae urine isolates from a national sample of home-based primary care patients with dementia. Datta, R., Pirruccio, G., Fried, TR., et al.[2023]

A systematic review of 5 studies found that the prevalence of adverse drug events (ADEs) in older inpatients with dementia is alarmingly high at 81.5%, indicating a significant safety concern for this population.

The prevalence of adverse drug reactions (ADRs) varied between 12.7% and 24.0%, highlighting the need for better assessment methods and tailored tools to prevent these reactions in older patients with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of adverse drug events and adverse drug reactions in hospital among older patients with dementia: A systematic review. Sakiris, MA., Sawan, M., Hilmer, SN., et al.[2021]

Acute renal failure was identified as the most common adverse drug reaction (ADR) in dementia patients, leading to longer hospital stays (median of 9 days for ADR-related admissions compared to 6 days for non-ADR admissions).

Patients with dementia who experienced ADRs had significantly higher in-hospital mortality and increased risk of subsequent ADR-related admissions within 30, 60, and 90 days, highlighting the need for careful medication management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse clinical outcomes associated with drug-related hospitalizations in people with dementia. Zaidi, AS., Peterson, GM., Curtain, CM., et al.[2023]

In a study of 1332 patients with Alzheimer's disease or other dementias in France, the prevalence of adverse drug reactions (ADRs) was found to be 5.0%, with serious ADRs occurring in 31.9% of cases, highlighting the potential risks associated with medication in this population.

The most common ADRs were gastrointestinal, central nervous system, and psychiatric disorders, with anti-dementia and psychotropic drugs being the most frequently implicated, indicating a need for careful monitoring and prescribing practices in patients with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in patients with Alzheimer's disease and related dementia in France: a national multicentre cross-sectional study. Laroche, ML., Perault-Pochat, MC., Ingrand, I., et al.[2013]

A systematic review of 26 studies found that the prevalence of potentially inappropriate prescribing in older people with dementia ranges from 14% to 74%, highlighting a significant risk for adverse events in this population.

The Beers criteria were the most commonly used tool for identifying inappropriate prescriptions, but many studies did not utilize the full criteria, suggesting a need for more standardized and comprehensive application of these tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying potentially inappropriate prescribing in older people with dementia: a systematic review. Hukins, D., Macleod, U., Boland, JW.[2022]

A multicomponent intervention aimed at improving the management of suspected urinary tract infections (UTIs) and lower respiratory infections (LRIs) in nursing home residents with advanced dementia did not significantly reduce the overall use of antimicrobials, despite high adherence to training among healthcare practitioners.

However, the intervention did lead to a significant reduction in the use of chest radiography for diagnosing LRIs, indicating some positive impact on the management of these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Trial to Reduce Antimicrobial Use in Nursing Home Residents With Alzheimer Disease and Other Dementias (TRAIN-AD): A Cluster Randomized Clinical Trial. Mitchell, SL., D'Agata, EMC., Hanson, LC., et al.[2022]

The TRAIN-AD trial successfully achieved high participation rates in training activities among nursing home providers, with 93% of the 380 participants attending at least one training session.

Factors such as being a nurse, working in higher quality facilities, and being present at the start of the program were associated with greater adherence to the training components, indicating areas for improvement in future training efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Provider adherence to training components from the Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD) intervention. Hendricksen, M., Loizeau, AJ., Habtemariam, DA., et al.[2022]

Upon admission to nursing homes, 40.1% of residents with dementia were prescribed cholinesterase inhibitors (ChEIs) and memantine, with higher usage in those with mild to moderately severe dementia compared to those with advanced dementia.

After 3 months, the use of ChEIs and memantine decreased significantly, with residents having advanced dementia being 1.44 times more likely to reduce their medication compared to those with less severe dementia, highlighting a need for further research on medication optimization in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholinesterase inhibitor and memantine use in newly admitted nursing home residents with dementia. Parsons, C., Briesacher, BA., Givens, JL., et al.[2021]

In a study of 430 nursing home residents with advanced dementia, 13.7% received antimicrobials in the two months prior to the study, highlighting a significant issue of antimicrobial use in this vulnerable population.

Facility characteristics, such as having a full-time nurse practitioner or physician assistant and fewer established infectious disease practices, were linked to higher rates of antimicrobial prescriptions, suggesting that improving these practices could help reduce unnecessary antimicrobial use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Antimicrobial Use in Nursing Home Residents With Advanced Dementia. Hendricksen, M., Habtemariam, D., D'Agata, EMC., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8276127/

The Trial to Reduce Antimicrobial Use in Nursing Home ... An intervention to improve infection management did not significantly reduce antimicrobial use among nursing home residents with advanced dementia.

2. withpower.com withpower.com/trial/phase-4-alzheimer-disease-10-2023-69e29

Reducing Antibiotic Use for Dementia (TRAIN-AD 2 Trial) This study will evaluate the effectiveness of a clinician champion intervention over 24 months to reduce the use of potentially inappropriate medications (PIMs) ...

3. ltcdatacooperative.org ltcdatacooperative.org/pages/current-research.aspx

Current Research Building on this work, the objective is to conduct TRAIN-AD 2.0; a larger, fully pragmatic trial to evaluate the effectiveness of the TRAIN-AD intervention to ...

4. researchgate.net researchgate.net/publication/353199303_The_Trial_to_Reduce_Antimicrobial_Use_in_Nursing_Home_Residents_With_Alzheimer_Disease_and_Other_Dementias_TRAIN-AD_A_Cluster_Randomized_Clinical_Trial

The Trial to Reduce Antimicrobial Use in Nursing Home ... The Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD) was a cluster RCT ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6794759/

The trial to reduce antimicrobial use in nursing home ... TRAIN-AD is the first cluster RCT testing a multicomponent intervention to improve infection management in NH residents with advanced dementia.

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/17/NCT03244917/SAP_001.pdf

TRAIN-AD Statistical Analysis Plan - CONFIDENTIAL To conduct a cluster RCT of an intervention to improve infection management among. 410 residents with advanced dementia (N=205/arm) residing in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2451865422000308

Provider adherence to training components from the Trial ... This report examines facility and provider characteristics associated with greater adherence to training components of the TRAIN-AD intervention.