Clinical trial NCT05387096: OPTImization of Medication by Transdisciplinary Assessment of Drug Treatment in Elderly Hospitalized Patients
Official title: OPTImization of Medication by Transdisciplinary Assessment of Drug Treatment in Elderly Hospitalized Patients: Application of a Definitive Intervention by Physicians or Clinical Pharmacists
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Multimorbidity
Polypharmacy
Keywords: inappropriate prescribing
multimorbidity
polypharmacy
hospital admission
older people
frail elderly
medication therapy management
STOPP/START
Lead sponsor: University College Cork
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: University Hospital Waterford
First posted: 2022-05-24
Enrollment: 642
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized controlled clinical trial is proposed in which it is anticipated to randomize 3 x 463 patients to one of 3 groups: (a) standard pharmaceutical care, or (b) trained physician-implemented DI, or (c) clinical pharmacist-implemented DI.
Primary purpose: PREVENTION

Brief summary: This study is being done to find out if a multi-faceted intervention designed to optimize medication in hospitalized older people with multiple chronic medical conditions exposed to multiple medications can reduce unplanned hospital readmission and emergency department attendance compared to current usual medication management. The study intervention aims to minimize potentially inappropriate medications in a structured way and involves follow up with patients and GPs. Patients will be allocated equally to (i) standard medication management (control arm) or (ii) trained physician-delivered intervention or (iii) clinical pharmacist-delivered intervention.

Detailed description: Background:

Recurrent hospitalization and unplanned emergency department (ED) attendance resulting from potentially inappropriate medication is an increasingly common phenomenon in older people with multi-morbidity and associated polypharmacy. With a growing older population with multi-morbidity/polypharmacy, there is a pressing need to address the increasing challenge of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) and associated problems that accentuate adverse drug reactions/events and avoidable excess morbidity. There is also an imperative to curb excess healthcare expenditure related to preventable medication-related problems.

Objective:

To test the clinical and economic impact of a multi-faceted medication optimization definitive intervention on avoidable rehospitalization and unscheduled ED attendance in multi-morbid patients aged ≥ 70 years hospitalized with acute illness.To test the clinical and economic impact of a multi-faceted medication optimization definitive intervention (DI) on avoidable rehospitalization and unscheduled ED attendance in multi-morbid patients aged ≥ 70 years hospitalized with acute illness.

Design:

A randomized controlled clinical trial is proposed in which it is anticipated to randomize 3 x 463 patients to one of 3 groups: (a) standard pharmaceutical care, or (b) trained physician-implemented DI, or (c) clinical pharmacist-implemented DI.

Setting: Acute care environment in 3 large tertiary referral teaching hospitals with similar custom and practice relating to management of older people with acute illness.

Participants: Patients aged ≥ 70 years with multi-morbid illness i.e. ≥ 3 chronic medical conditions and associated polypharmacy i.e. ≥ 5 daily prescription medications admitted with acute unselected illness.

Intervention:

The definitive multi-faceted intervention will consist of the following components:modified structured history of medication (SHiM), Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) screening for PIMs and PPOs using STOPP/START version 3.0, drug-drug interaction screening using Stockley's Drug Interaction Checker, face-to-face consultation with attending hospital physicians to discuss PIMs, PPOs, interactions and other issues, pre-discharge medication review and adjustment, detailed medication adjustment discharge report to patients' general practitioners (GPs), post-discharge follow-up contact with patients' GPs and community pharmacists at 1 week and 1 and 3-6 months post-discharge.

Study Population:

OPTIMATE will focus on patients admitted with acute medical or surgical illness to Cork University Hospital, University Hospital Waterford and Ghent University Hospital. Patients to be screened for enrolment are those admitted primarily under the care of specialist departments other than geriatric medicine.

Data Collection:

All OPTIMATE trial data will be collected electronically and entered on a bespoke trial proforma. Once verified as fully correct and complete, all individual participant trial data will be stored on a fully secure clinical trial database.

Statistical Analysis:

Treatment effects for each of the two active intervention arms (versus control) in terms of binary outcomes (e.g. readmission) will be estimated using logistic regression, while Health Related QoL (EQ-5D 5L) will be analyzed using ordinal regression with a logit link function (i.e. a proportional odds model). We will report two models for each outcome: one adjusted for centre and admitting service type; and another further adjusted for centre, age (years), sex, number of comorbidities at baseline, and number of prescribed medications at baseline. Effect estimates will be reported as odds-ratios with 95% confidence intervals and exact p-values. There will be no correction for multiplicity, but we will report results for all outcomes regardless of the result and provide enough information for the reader to make whatever corrections they may consider appropriate. Equivalence tests comparing the two active arms (for each outcome) will be done using a "two one-sided tests" procedure based on a 90% confidence interval (which equates to a 5% type 1 error rate). All analyses will be conducted on an intention-to-treat basis and will be conducted under the quality system and SOPs of the HRB CRF-C Statistics and Data Analysis Unit. A complete statistical analysis plan (SAP) will be pre-registered on the Open Science Framework prior to patient recruitment database lock. Any necessary deviations from this SAP will be documented and explained in the trial report. There will be only one single trial data analysis at the end of the project. All reporting will be carried out in accordance with CONSORT guidelines for clinical trials.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 70years
2. 3 or more chronic conditions.
3. ≥ 5 daily medications pre-admission, all medications taken for at least 4 weeks continuously.
4. Can speak and understand English (in the two Irish medical centres), and Dutch or French in Ghent University Hospital (Ghent is predominantly Dutch-speaking).
5. Can give informed consent or give witnessed verbal consent or have a suitable proxy who can give informed assent on the patient's behalf.
6. Agrees to follow-up contact post-discharge up to 180 days post-randomization.
7. Agrees to primary researcher contacting the GP and community pharmacist post-discharge.

Exclusion Criteria:

1. Terminal illness.
2. Severe dementia and clearly unable to understand the purpose of the trial or give consent to participation.
3. Severe communication disorder, making informed consent impossible.
4. Likely to be discharged from hospital within 48 hours of arrival.
5. Intensive Care Unit (ICU) admission.
6. Primary psychiatric presenting illness.
7. Unavailable for post-discharge follow-up for any reason.
8. Non-accidental poisoning.
9. Previous participation in medication optimization trials.
10. Active participation in another clinical trial
11. Infectious illness requiring strict isolation (including COVID-19 infection) blocking access of the primary researcher to the patient for enrolment.
12. End-stage renal, liver or lung disease requiring organ replacement therapy.
13. Admitted under the care of specialists in Clinical Pharmacology, Palliative Medicine, Clinical Oncology or Haematology.
14. Admitted under the care of specialists in Geriatric Medicine in Ghent University Hospital.
15. Trial participation refusal.

Primary outcomes:
measure: Unscheduled readmission to hospital.
timeFrame: At day 30 post-discharge.
measure: Emergency Department attendance.
timeFrame: At day 30 post-discharge.
measure: Composite endpoint 1
timeFrame: At day 30 post-discharge.
measure: Unscheduled readmission to hospital.
timeFrame: At between days 90 and 180 post-discharge.
measure: Emergency Department attendance.
timeFrame: At between days 90 and 180 post-discharge.
measure: Composite endpoint 2
timeFrame: At between days 90 and 180 post-discharge.
Secondary outcomes:
measure: Quality of life measured by EuroQol quality of life 5 dimensional 5 level instrument (incorporating pain control)
timeFrame: At day 30 post-discharge.
measure: Quality of life measured by EuroQol quality of life 5 dimensional 5 level instrument
timeFrame: At between days 90 and 180 post-discharge.
measure: All-cause mortality
timeFrame: At day 30 post-discharge.
measure: All-cause mortality
timeFrame: At between days 90 and 180 post-discharge.
measure: Occurrence of first admission to residential care facility for long-term nursing care
timeFrame: At day 30 post-discharge.
measure: Occurrence of first admission to residential care facility for long-term nursing care
timeFrame: At between days 90 and 180 post-discharge.
Other outcomes:
measure: Quality Life Adjusted Year (QALY)
timeFrame: At between days 90 and 180 post-discharge.
measure: Cost per hospital readmission avoided
timeFrame: At between days 90 and 180 post-discharge.
measure: Cost per ED attendance avoided
timeFrame: At between days 90 and 180 post-discharge.
measure: Unscheduled readmission to hospital within 180 days of discharge
timeFrame: At between days 90 and 180 post-discharge.
measure: Composite endpoint of readmission to hospital or emergency department attendance within 180 days of discharge
timeFrame: At between days 90 and 180 post-discharge.
Locations:
city: Gent
country: Belgium
facility: Ghent University Hospital
city: Cork
country: Ireland
facility: Cork University Hospital
city: Waterford
country: Ireland
facility: University Hospital Waterford
Study officials:
affiliation: University College Cork
name: Denis O'Mahony, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Al Hamid A, Ghaleb M, Aljadhey H, Aslanpour Z. A systematic review of hospitalization resulting from medicine-related problems in adult patients. Br J Clin Pharmacol. 2014 Aug;78(2):202-17. doi: 10.1111/bcp.12293.
citation: Blum MR, Sallevelt BTGM, Spinewine A, O'Mahony D, Moutzouri E, Feller M, Baumgartner C, Roumet M, Jungo KT, Schwab N, Bretagne L, Beglinger S, Aubert CE, Wilting I, Thevelin S, Murphy K, Huibers CJA, Drenth-van Maanen AC, Boland B, Crowley E, Eichenberger A, Meulendijk M, Jennings E, Adam L, Roos MJ, Gleeson L, Shen Z, Marien S, Meinders AJ, Baretella O, Netzer S, de Montmollin M, Fournier A, Mouzon A, O'Mahony C, Aujesky D, Mavridis D, Byrne S, Jansen PAF, Schwenkglenks M, Spruit M, Dalleur O, Knol W, Trelle S, Rodondi N. Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial. BMJ. 2021 Jul 13;374:n1585. doi: 10.1136/bmj.n1585.
citation: Cardwell K. Reducing medication errors and transitions of care. Age Ageing. 2020 Jul 1;49(4):537-539. doi: 10.1093/ageing/afaa065. No abstract available.
citation: Dalton K, O'Mahony D, O'Sullivan D, O'Connor MN, Byrne S. Prescriber Implementation of STOPP/START Recommendations for Hospitalised Older Adults: A Comparison of a Pharmacist Approach and a Physician Approach. Drugs Aging. 2019 Mar;36(3):279-288. doi: 10.1007/s40266-018-0627-2.
citation: Drenth-van Maanen AC, Spee J, van Hensbergen L, Jansen PA, Egberts TC, van Marum RJ. Structured history taking of medication use reveals iatrogenic harm due to discrepancies in medication histories in hospital and pharmacy records. J Am Geriatr Soc. 2011 Oct;59(10):1976-7. doi: 10.1111/j.1532-5415.2011.03610_11.x. No abstract available.
citation: El Morabet N, Uitvlugt EB, van den Bemt BJF, van den Bemt PMLA, Janssen MJA, Karapinar-Carkit F. Prevalence and Preventability of Drug-Related Hospital Readmissions: A Systematic Review. J Am Geriatr Soc. 2018 Mar;66(3):602-608. doi: 10.1111/jgs.15244. Epub 2018 Feb 22.
citation: Hyttinen V, Jyrkka J, Valtonen H. A Systematic Review of the Impact of Potentially Inappropriate Medication on Health Care Utilization and Costs Among Older Adults. Med Care. 2016 Oct;54(10):950-64. doi: 10.1097/MLR.0000000000000587.
citation: Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother. 2008 Jul;42(7):1017-25. doi: 10.1345/aph.1L037. Epub 2008 Jul 1.
citation: Kuhn-Thiel AM, Weiss C, Wehling M; FORTA authors/expert panel members. Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging. 2014 Feb;31(2):131-40. doi: 10.1007/s40266-013-0146-0.
citation: Laugaland K, Aase K, Barach P. Interventions to improve patient safety in transitional care--a review of the evidence. Work. 2012;41 Suppl 1:2915-24. doi: 10.3233/WOR-2012-0544-2915.
citation: Lavan A, Eustace J, Dahly D, Flanagan E, Gallagher P, Cullinane S, Petrovic M, Perehudoff K, Gudmondsson A, Samuelsson O, Sverrisdottir A, Cherubin A, Dimitri F, Rimland J, Cruz-Jentoft A, Velez-Diaz-Pallares M, Lozano Montoya I, Soiza RL, Subbarayan S, O'Mahony D. Incident adverse drug reactions in geriatric inpatients: a multicentred observational study. Ther Adv Drug Saf. 2018 Jan;9(1):13-23. doi: 10.1177/2042098617736191. Epub 2017 Oct 24.
citation: Leendertse AJ, Van Den Bemt PM, Poolman JB, Stoker LJ, Egberts AC, Postma MJ. Preventable hospital admissions related to medication (HARM): cost analysis of the HARM study. Value Health. 2011 Jan;14(1):34-40. doi: 10.1016/j.jval.2010.10.024.
citation: McAuliffe LH, Zullo AR, Dapaah-Afriyie R, Berard-Collins C. Development and validation of a transitions-of-care pharmacist tool to predict potentially avoidable 30-day readmissions. Am J Health Syst Pharm. 2018 Feb 1;75(3):111-119. doi: 10.2146/ajhp170184.
citation: Moriarty F, Bennett K, Cahir C, Kenny RA, Fahey T. Potentially inappropriate prescribing according to STOPP and START and adverse outcomes in community-dwelling older people: a prospective cohort study. Br J Clin Pharmacol. 2016 Sep;82(3):849-57. doi: 10.1111/bcp.12995. Epub 2016 Jun 9.
citation: O'Brien GL, O'Mahony D, Gillespie P, Mulcahy M, Walshe V, O'Connor MN, O'Sullivan D, Gallagher J, Byrne S. Cost-Effectiveness Analysis of a Physician-Implemented Medication Screening Tool in Older Hospitalised Patients in Ireland. Drugs Aging. 2018 Aug;35(8):751-762. doi: 10.1007/s40266-018-0564-0.
citation: O'Connor MN, O'Sullivan D, Gallagher PF, Eustace J, Byrne S, O'Mahony D. Prevention of Hospital-Acquired Adverse Drug Reactions in Older People Using Screening Tool of Older Persons' Prescriptions and Screening Tool to Alert to Right Treatment Criteria: A Cluster Randomized Controlled Trial. J Am Geriatr Soc. 2016 Aug;64(8):1558-66. doi: 10.1111/jgs.14312. Epub 2016 Jul 1.
citation: O'Mahony D, O'Sullivan D, Byrne S, O'Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015 Mar;44(2):213-8. doi: 10.1093/ageing/afu145. Epub 2014 Oct 16.
citation: O'Mahony D, Gudmundsson A, Soiza RL, Petrovic M, Cruz-Jentoft AJ, Cherubini A, Fordham R, Byrne S, Dahly D, Gallagher P, Lavan A, Curtin D, Dalton K, Cullinan S, Flanagan E, Shiely F, Samuelsson O, Sverrisdottir A, Subbarayan S, Vandaele L, Meireson E, Montero-Errasquin B, Rexach-Cano A, Correa Perez A, Lozano-Montoya I, Velez-Diaz-Pallares M, Cerenzia A, Corradi S, Soledad Cotorruelo Ferreiro M, Dimitri F, Marinelli P, Martelli G, Fong Soe Khioe R, Eustace J. Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial. Age Ageing. 2020 Jul 1;49(4):605-614. doi: 10.1093/ageing/afaa072.
citation: O'Sullivan D, O'Mahony D, O'Connor MN, Gallagher P, Gallagher J, Cullinan S, O'Sullivan R, Eustace J, Byrne S. Prevention of Adverse Drug Reactions in Hospitalised Older Patients Using a Software-Supported Structured Pharmacist Intervention: A Cluster Randomised Controlled Trial. Drugs Aging. 2016 Jan;33(1):63-73. doi: 10.1007/s40266-015-0329-y.
citation: Oscanoa TJ, Lizaraso F, Carvajal A. Hospital admissions due to adverse drug reactions in the elderly. A meta-analysis. Eur J Clin Pharmacol. 2017 Jun;73(6):759-770. doi: 10.1007/s00228-017-2225-3. Epub 2017 Mar 1.
citation: Ravn-Nielsen LV, Duckert ML, Lund ML, Henriksen JP, Nielsen ML, Eriksen CS, Buck TC, Pottegard A, Hansen MR, Hallas J. Effect of an In-Hospital Multifaceted Clinical Pharmacist Intervention on the Risk of Readmission: A Randomized Clinical Trial. JAMA Intern Med. 2018 Mar 1;178(3):375-382. doi: 10.1001/jamainternmed.2017.8274.
citation: Thomsen LA, Winterstein AG, Sondergaard B, Haugbolle LS, Melander A. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care. Ann Pharmacother. 2007 Sep;41(9):1411-26. doi: 10.1345/aph.1H658. Epub 2007 Jul 31.
citation: Thompson K, Kulkarni J, Sergejew AA. Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr Res. 2000 May 5;42(3):241-7. doi: 10.1016/s0920-9964(99)00130-9.
citation: Weir DL, Lee TC, McDonald EG, Motulsky A, Abrahamowicz M, Morgan S, Buckeridge D, Tamblyn R. Both New and Chronic Potentially Inappropriate Medications Continued at Hospital Discharge Are Associated With Increased Risk of Adverse Events. J Am Geriatr Soc. 2020 Jun;68(6):1184-1192. doi: 10.1111/jgs.16413. Epub 2020 Mar 31.
citation: Xing XX, Zhu C, Liang HY, Wang K, Chu YQ, Zhao LB, Jiang C, Wang YQ, Yan SY. Associations Between Potentially Inappropriate Medications and Adverse Health Outcomes in the Elderly: A Systematic Review and Meta-analysis. Ann Pharmacother. 2019 Oct;53(10):1005-1019. doi: 10.1177/1060028019853069. Epub 2019 May 25.
citation: Cullinan S, O'Mahony D, Byrne S. Application of the structured history taking of medication use tool to optimise prescribing for older patients and reduce adverse events. Int J Clin Pharm. 2016 Apr;38(2):374-9. doi: 10.1007/s11096-016-0254-0. Epub 2016 Jan 21.