OPtimising thERapy to Prevent Avoidable Hospital Admissions in the Multimorbid Older People

3 or More Chronic Conditions for 6 Months or Longer Clinical Trial

— OPERAM  

Official title:

OPERAM: OPtimising thERapy to Prevent Avoidable Hospital Admissions in the Multimorbid Older People: a Cluster Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02986425
• Other study ID #: U1111-1181-9400
• Status: Completed
• Phase: N/A
• Start date: December 2016
• Est. completion date: October 2019

Study information

• Verified date: August 2020
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this Randomised Controlled Trial (RCT) is to evaluate whether the Systematic Tool to Reduce Inappropriate Prescribing (STRIP) including STRIP assistant (STRIPA) implemented by an appropriately qualified team will lead to an improvement in clinical and economic outcomes among patients aged 70 years and more with multimorbidity and polypharmacy.

Description:

Background:

Drug-related morbidity and mortality is an increasing problem in European healthcare systems. Multimorbidity, polypharmacy and old age are important risk factors for drug-related hospital admissions (DRA). The reported incidence of DRAs in the elderly may be as high as 30% of all acute cases, and about half of DRAs are likely to be preventable. They are mainly related to prescribing problems and non-compliance with drug regimens. A significant proportion of healthcare costs are spent on unnecessary interventions and inappropriate medications. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) is a structured method to perform a medication review to optimise pharmacotherapy.

Design:

European multi-centre, cluster randomised, controlled trial of people aged 70 years or older, with multimorbidity and polypharmacy, being on an ambulatory visit or on a hospital stay in one of the four participating centres in Ireland, Belgium, Switzerland and the Netherlands. A cluster is defined around a treating physician, i.e. the treating physician is randomised and defines the allocation of his patients. Clusters of patients will be randomised to the intervention arm receiving STRIP for optimising therapy or to the control arm undergoing usual clinical care. The patients of physicians who are allocated to the intervention group will undergo a systematic drug review and pharmacotherapy optimisation by a physician and a pharmacist using STRIP, including the STRIPA software. That provides the research team with a recommendation of changes in the patient's medication. Based on STRIPA recommendation and agreement on changes to the patients' pharmacotherapy between the team of the research physician and pharmacist and the prescribing physician, will the patient receive structured counselling about his/her medication; general practitioners will receive a report. Patients will be further followed for 1 year with follow-up phone calls after 2, 6 and 12 months. For the purpose of this trial, all hospitalisations during follow-up of participants will be adjudicated to assess their relationship to adverse drug events.

Objectives:

The primary objective is to assess the effect of a structured medication review and pharmacotherapy optimisation using the STRIP on drug-related hospitalisations (DRA) caused by over-, mis-, and underuse or over-, mis-, and underprescribing of medications.

Secondary objectives will be to assess the impact of pharmacotherapy optimisation on falls, quality of life, polypharmacy, medication changes, activities of daily living, and mortality.

Statistical considerations:

80 clusters with a cluster size ranging from 12 to 38 participants will be included. Therefore, 2000 patients, 1000 patients in each arm, will be recruited over 18 months. The trial will have 80% power with this sample size.

The primary analysis will be an intention-to-treat (ITT) analysis, whereby all randomised patients will be included in the group they were allocated to.

The primary outcome of drug-related admission will be analysed using a random-effects competing risk proportional hazards model that accounts for the competing risk of death and for clustering of data within centre and prescribing physician.

Overall survival will be analysed using a random-effects Cox proportional hazards model that accounts for clustering of data within centre and prescribing physician. The analysis of falls will also take into account the competing risk of death. Continuous outcomes will be analysed by random-effects linear regression. All effect measures will be accompanied by 95% confidence intervals and all p-values will be two-sided.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2009
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

• People 70 years of age or older

• Multimorbidity: 3 or more coexistent chronic conditions defined by 3 distinct International Classification of Diseases (ICD-10) codes with an estimated duration of 6 months or more or based on a clinical decision

• Polypharmacy i.e. five or more different regular drugs (defined as authorised medications with registration numbers) for more than 30 days.

• In inpatient: Estimated minimal length of stay within the cluster is sufficient to apply the intervention

• If outpatient: prescribing physician has GP function and has a planned appointment to conduct intervention

Exclusion Criteria:

• Inability to provide informed consent or to obtain informed consent from a proxy for patients with cognitive impairment

• Direct admission to palliative care (< 24h after admission)

• Has passed or will pass a systematic structured drug review during this hospitalisation or within the last two months

Related Conditions & MeSH terms

• 3 or More Chronic Conditions for 6 Months or Longer
• 5 or More Regular Drugs

Intervention

Other:
• STRIP intervention
The STRIP intervention consists of 9 steps: structured history taking of medication recording medication and diagnoses in STRIPA structured drug review based on the STRIPA with the integrated Screening Tool of Older Person's Prescriptions (STOPP)/ Screening Tool to Alert Doctors to the Right Treatment (START) criteria communication and discussion of the structured drug review with prescribing physician with possible adaptation of the recommendation shared decision-making with the patient with possible adaptation of the recommendation optional revision based on new accumulating data during hospitalisation (e.g. new diagnoses, adverse drug reactions) generation of general practioner (GP) report delivery of the report to the patient and to the GP (optional additional direct communication) follow-up
• Control
Standard care in the department where the trial is conducted. To keep the patients and the blinded team members blinded one questionnaire will be conducted by the intervention team in both arms. This is considered a SHAM intervention.

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Bruxelles
Ireland	Dept. of Medicine (Geriatrics), University College Cork	Cork
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Switzerland	University of Bern and University Hospital Bern (Inselspital)	Bern

Sponsors (10)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Cork University Hospital, European Commission, State Secretariat for Education Research and Innovation, Switzerland, UMC Utrecht, Université Catholique de Louvain, University of Basel, University of Bern, Utrecht University

Countries where clinical trial is conducted

Belgium,  Ireland,  Netherlands,  Switzerland, 

References & Publications (4)

Gillespie U, Alassaad A, Henrohn D, Garmo H, Hammarlund-Udenaes M, Toss H, Kettis-Lindblad A, Melhus H, Mörlin C. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial. Arch Intern Med. 2009 May 11;169(9):894-900. doi: 10.1001/archinternmed.2009.71. — View Citation

Howard RL, Avery AJ, Slavenburg S, Royal S, Pipe G, Lucassen P, Pirmohamed M. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2007 Feb;63(2):136-47. Epub 2006 Jun 26. Review. — View Citation

Laws MB. Adverse drug reactions as cause of admission to hospital: definition of adverse drug reactions needs to include overdose. BMJ. 2004 Aug 21;329(7463):459-60; author reply 460. — View Citation

Leendertse AJ, Egberts AC, Stoker LJ, van den Bemt PM; HARM Study Group. Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands. Arch Intern Med. 2008 Sep 22;168(17):1890-6. doi: 10.1001/archinternmed.2008.3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients with confirmed DRA after discharge from the index hospitalisation	The primary outcome is defined as the first confirmed DRA after discharge from the index hospitalisation within a period of 12 months.; Confirmation of a drug-related hospital admission will be assessed by an independent and blinded adjudication committee (per site). Prolongation of the index hospitalisation and prolongation of any following hospitalisations will not be adjudicated for drug-relatedness. Adjudication is done according to specific guidelines.	12 months
Secondary	Number of survivors	Including causes of death	12 months
Secondary	Number of cancer deaths	As subgroup of all deaths this is considered a negative control outcome.	12 months
Secondary	Number of patients with hospitalisations	Detected during the follow-up phone calls	12 months
Secondary	Number of patients with falls	Detected during the follow-up phone calls	12 months
Secondary	Patients' degree of poly-pharmacy	Degree of polypharmacy, defined as the number of regular long-term medications	12 months
Secondary	Patients' quality of life	Quality of life as measured by the visual analogue scale of the European Quality of Life-5 Dimensions instrument (EQ-5D)	12 months
Secondary	Patients' level of pain/discomfort	Item form EQ-5D questionnaire	12 months
Secondary	Patients' basic activities of daily living	Measured by questionnaire Barthel Index Basic Activities of Daily Living (ADL)	12 months
Secondary	Patients' drug compliance	Measured by the Morisky Medication Adherence Questionnaire (MMAS-8)	12 months
Secondary	Number of clinically significant drug-drug interactions	Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected	2 months
Secondary	Number of drug overuse	Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected	2 months
Secondary	Number of drug underuse	Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected	2 months
Secondary	Number of potentially inappropriate medications	Assessed based on using STRIPA including the list of diagnosis form the Index Hospitalisation and the updated medication list at follow-up. Assessment will be done at the end of the trial, when all data was collected	2 months
Secondary	Number of patients with a serious adverse event		12 months