Clinical trial NCT03741283: Optimisation of Nutrition and Medication for Acutely Admitted Older Medical Patients
Official title: Optimisation of Nutrition and Medication for Acutely Admitted Older Medical Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Aging
Malnutrition
Drug Prescribing
Keywords: Medicines optimisation
Multimodal interventions
Inflammation
Emergency Service, Hospital
Pharmacogenetics
Renal function
Food intake
Quality of life
Polypharmacy
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: Clinical Research Centre
name: Region Hovedstadens Apotek
name: Udviklings- og forskningspuljen, Danske Regioner og Sundhedskartellet
name: Region Capital Denmark
name: Regionernes Lægemiddelorganisation
First posted: 2018-11-14
Enrollment: 193
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Malnutrition and inappropriate medication prescribing are highly prevalent among acutely admitted older medical patients leading to re-admissions, frailty, poor physical, performance compromised quality of life and mortality. Thus, the aim of this study is to optimise the nutrition and medication in older medical patients admitted to an acute care department at admission and up to 16 weeks after discharge. Participants in the intervention group receives a medication review and participants with malnutrition or risk of malnutrition additionally receive a transitional multimodal intervention. The control group receives standard care.

Detailed description: The OptiNAM study is designed as a single-blinded randomised controlled trial starting upon admission and continues till 16 weeks after discharge. The trial has five sub-studies with three independent primary endpoints, all with individual sample size calculations.

The study consists of an intervention group and a control group. The control group receives standard care.

Patients that meet all inclusion criteria and none of the exclusion criteria are invited to participate. After signing a written informed consent, the participants are block randomised to either the intervention or control group.

The intervention group receives a personalised rehabilitation program, which is described below. Outcome measures are performed at baseline, week 8 and week 16 after after discharge, cf. section regarding outcome measures.

Sub study 1, Malnutrition:

As malnutrition among older patients has multifactorial etiology sub-study 1 investigates the effects of a multimodal transitional intervention on quality of life in acutely admitted older patients with malnutrition or risk of malnutrition (according to the Mini Nutritional Assessment - Short Form) from baseline (admission day) and 16 weeks after discharge compared to standard care. The intervention includes a medication review (cf. sub-study 2), a dietetic intervention and if clinical relevant physiotherapeutic-, occupational-, geriatric- and/or odontological intervention. It is secondary hypothesised that a multimodal intervention compared to standard care may improve the quality of life, nutritional status, energy- and protein intake, symptoms which compromise nutritional intake, physical performance, cognitive function, frailty, re-admissions, inflammation and biomarkers. A cost-benefit analysis will be conducted.

Dietetic intervention: The study subjects receives a personal diet plan during admission. The diet plan is reviewed at discharge by a dietician. To ensure optimal energy- and protein intake after discharge, a community-based dietician visit the participants for one hour in week 1, 2, 4 and 8.

Physiotherapeutic intervention: Participants with low ability to perform groceries shopping, cooking and/or eating are offered a community-based strength, balance and endurance training after discharge if they also have low muscle strength in the lower extremities. The training sessions are based on algorithms, have a duration of one hour, and are offered twice a week for 16 weeks after discharge.

Occupational intervention, Dysphagia: If relevant (EAT-10 score \>=3), a hospital-based occupational therapist review and treat the dysphagia based on the Facial Oral Tract Therapy (FOTT) principle during admission. During the first week after discharge a community-based occupational therapist continues with the treatment. A maximum of two weekly visits of one hour throughout the interventions period is offered.

Occupational Intervention, low Ability to perform Activities of Daily Living (ADL): If the participant has low ability to perform grocery shopping, cooking and eating (evaluated by Functional Recovery Score \<=2) then a community-based occupational therapist visit the participant during the first two weeks after discharge to evaluate the quality of activities of daily living. If relevant, and if there is a rehabilitation potential, seven visits of one hour is offered during the 16 weeks after discharge.

Geriatric intervention: If relevant (a Mini Geriatric Depression Score \>=2), a geriatric physician conducts a clinical assessment of depression during admission and initiate treatment if necessary.

Odontological intervention: If relevant (participant reported pain in mouth, difficulties chewing or xerostomia), a dentist evaluate the dental status and oral health during admission, and if necessary encourage the participant to consult a dentist after discharge. If a participant shows insufficient oral hygiene a dental hygienist visits the participant after discharge twice during after discharge.

Sub-study 2, Medication optimisation:

Medication prescription for older patients is challenging and may be attributed to marked inter-individual variations in general health, comorbidities, organ function, pharmacokinetic and pharmacodynamic properties, biological age and physical performance. Thus, the "one size fits all" approach is probably inappropriate in older patients. The aim of sub-study 2 is to investigate the investigate the effect of an inter-professional conducted medication review during admission in an acute care department regardless of the nutritional status in the study participant, thus all subjects in the intervention group receive a medication review. It is hypothesized that inter-professional conducted medication reviews reduce the Medication Appropriateness Index score (MAI score) in the intervention group eight weeks after discharge compared to the control group. It is secondary hypothesized that inter-professional conducted medication reviews improve: lack of medication prescribing for a condition/disease, inappropriate polypharmacy and suboptimal medication prescribing of high risk medications.

Sub-study 3, Accuracy of renal function estimates and the consequence for prescribing recommendations guidelines:

Accuracy in renal function estimates is essential for optimization of medication prescribing since 40 % of all medication or their active metabolites is renally excreted. Lack of medication prescribing and dose adjustment according to the renal function is common in older patients with renal impairment and can result in overdosing, adverse drug reactions, hospital admissions, reduced quality of life and mortality. The gold standard for measuring glomerular filtration rate (GFR) is an exogenous filtration marker. However, this method is costly, time consuming and thus impractical in a clinical setting. Therefore, GFR is often estimated on serum concentrations of an endogen biomarker. Sub-study 3 aim to investigate which biomarker(s) and equation most accurately estimate the GFR in older medical patients who have been acutely admitted.

Sub-study 4, Pharmacogenetic test on cytochrome 450 variations and its potential for optimization of medication prescribing:

Cytochrome 450 enzymes are responsible for metabolism of up to 80% of all medications. The enzyme complex is mainly found in liver but are also present in intestinal mucosa, skin, lungs, brain and kidneys. There are major genetic inter-individual differences in the activity of the CYP 450 complex, resulting in lack of therapeutic effects, lack of effect or adverse drug reactions. Insight into these genetic inter-individual differences via pharmacogenetic tests possess a potential in optimization of medication prescribing with regard to therapeutic effects, compliance and risk of side effects. Thus, sub-study 4 wish to descriptively investigate the potential of pharmacogenetic test on cytochrome 450 variations.

Sub-study 5, Assessment of Frailty:

Frailty is a common clinical syndrome in older adults and defined as state of increased vulnerability resulting from decline in reserve capacity and function across multiple physiologic systems. Frailty affects the person's ability to cope with everyday life and leads to high risk for falls, disability, hospitalization and mortality. The frailty assessment is based on two different frailty scoring systems, Frieds "Frailty Phenotype" and Morley's "Frail Scale", examined at admission and 8 and 16 weeks after discharge. The purpose of the assessment is to evaluate which frailty measure is the best applicable in describing the patients and changes in their functional level. As there is no gold standard we use FI-Outref as an independent measure of frailty. FI-OutRef is a Frailty Index, based on standard admission laboratory test results Outside of the Reference interval.

Eligibility criteria: Inclusion Criteria:

* ≥65 years
* Acutely admitted medical patients
* Understand and speak Danish
* Caucasian
* Resident in Municipality: Brøndby, Hvidovre or Copenhagen

Exclusion Criteria:

* Unable to cooperate cognitively
* Terminal/suicidal patients
* Patients in isolation

Primary outcomes:
measure: Changes in quality of life score EuroQol- 5 Dimensions- 5 Levels (sub-study 1)
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Changes in Medication Appropriateness Index-score" (sub-study 2)
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Accuracy of renal function estimates (sub-study 3) - cystatin C
timeFrame: Baseline (admission day) or no later than 14 days after admission
Secondary outcomes:
measure: Walking speed to evaluate the development in physical performance
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Functional measurement to evaluate the development in physical performance
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Functional measurement to evaluate the development in physical performance
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Functional measurement to evaluate the development in physical performance
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Measure of physically active time and number of steps taken
timeFrame: Week 1, week 8 and week 16 after discharge
measure: Frailty assessment
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Frailty assessment
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Anthropometric measurement to monitor changes in bodyweight
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Cognitive test aiming to evaluate cognitive function
timeFrame: Baseline (admission day), week 8 and week 16
measure: Patient records
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Standard admission blood work
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Quality of life score, WHO-5
timeFrame: Baseline (admission day), week 8 and week 16
measure: Cognitive performance
timeFrame: Week 8 and week 16
measure: Cognitive performance
timeFrame: Week 8 and week 16
measure: Cognitive performance
timeFrame: Week 8 and week 16
measure: Cognitive performance
timeFrame: Week 8 and week 16
measure: Assessment of dietary intake after admission
timeFrame: Week 8 and week 16
measure: Evaluation of medication under-prescribing
timeFrame: Baseline (admission day), week 8 and week 16
measure: Inflammatory marker to evaluate the inflammatory state
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Polypharmacy
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Potentially inappropriate medication to elderly
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Acceptance of suggested changes in medications
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Accuracy of renal function estimates - all biomarkers
timeFrame: Baseline (admission day) or no later than 14 days after admission.
measure: Dosing discrepancies of renal risk medication
timeFrame: Baseline (admission day) or no later than 14 days after admission.
measure: Nutritional status
timeFrame: Baseline (admission day), week 8 and week 16.
measure: Intestinal microbiome composition
timeFrame: Baseline (admission day), week 8 and week 16 after discharge.
measure: Body composition
timeFrame: Baseline (admission day), daily through out admission, up to three weeks after admission during kidney function measurement, week 8 and week 16 after discharge.
measure: Body composition
timeFrame: Up to three weeks after admission during kidney function measurement
Other outcomes:
measure: Number and types of actionable gene variants - Pharmacogenetic test
timeFrame: Baseline (admission day)
measure: Number and types of recommended therapy changes -Pharmacogenetic test
timeFrame: Baseline (admission day)
measure: Health economy related to Sub-study 1
timeFrame: Baseline (admission day), week 8 and week 16 and 1 year after discharge
Locations:
city: Hvidovre
country: Denmark
facility: Amager & Hvidovre Hospital
state: Region Hovedstaden
Study officials:
affiliation: Hvidovre University Hospital
name: Ove Andersen, MD, PhD
role: STUDY_CHAIR
affiliation: Hvidovre University Hospital
name: Aino L. Andersen, MSc
role: PRINCIPAL_INVESTIGATOR
References: