Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials

doi:10.1016/j.pcad.2014.07.005

Progress in Cardiovascular Diseases

Volume 57, Issue 2, September–October 2014, Pages 144-151

https://doi.org/10.1016/j.pcad.2014.07.005 Get rights and content

Abstract

There is increasing momentum to measure frailty in clinical practice given its proven value as a predictor of outcomes, particularly in elderly patients with cardiovascular disease. The number of randomized clinical trials targeting frail older adults has been modest to date. Therefore, we systematically searched the ClinicalTrials.gov registry in order to review the frailty intervention trials that had been actively initiated or completed but not yet published. The interventions studied were exercise training in 2 trials, nutritional supplementation in 3 trials, combined exercise plus nutritional supplementation in 5 trials, pharmaceutical agents in 5 trials, multi-dimensional programs in 2 trials, and home-based services in 3 trials. Their respective study designs, populations, interventions, and planned outcomes are presented in this article.

Section snippets

Methods

The ClinicalTrials.gov registry was queried using the following search string: (frail OR frailty OR sarcopenic OR sarcopenia) AND (randomized). The “Interventional” filter was selected. The inclusion criteria for this review were: (1) randomized controlled trial, (2) ongoing or completed but not yet published, (3) population of older adults with frailty/pre-frailty or sarcopenia as determined by an objective assessment tool (broadly defined as a multi-item frailty scale such as Fried’s,⁵ low

Results

The search identified 265 entries, of which 20 met the inclusion criteria for this review (Table 1, Fig 2). The official status was not yet recruiting in 5 RCTs, recruiting in 6, active but not recruiting in 4, and completed but not yet published in 5. The frailty criteria used to determine eligibility were PPTs in 8 RCTs, Fried’s scale in 6, muscle mass with or without PPTs in 3, and other scales in 3. Five RCTs focused on individuals with a specific comorbidity: stable coronary artery

Discussion

One half of registered RCTs are evaluating exercise and/or nutrition, which have long been recognized as therapeutic cornerstones for frailty. These RCTs are all short-term in design, ranging from 3 to 6 months, and it remains to be seen whether this is sufficient time to reverse existing frailty and yield clinically detectable benefits. Regular exercise and physical activity have been shown to prevent or delay incident frailty.⁷ Two systematic reviews including frail and non-frail older adults

Statement of Conflict of Interest

All authors declare that there are no conflicts of interest.

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Cited by (54)

Protein and Exercise to Reverse Frailty in Older Men and Women Undergoing Transcatheter Aortic Valve Replacement: Design of the PERFORM-TAVR Trial
2024, Canadian Journal of Cardiology
Despite the high procedural success of transcatheter aortic valve replacement (TAVR), 2 out of 5 older adults report poor physical performance and health-related quality of life (HRQOL) in the ensuing months, particularly those with frailty. There has yet to be a trial examining the synergistic effects of exercise and protein supplementation to counteract frailty and improve patient-centred outcomes following TAVR. The PERFORM-TAVR trial is a multicentre parallel-group randomised clinical trial that is enrolling 200 frail older adults ≥ 70 years of age undergoing TAVR. Patients will be randomly allocated to 1 of 2 treatment groups: standard-of-care lifestyle education (control group) or protein-rich oral nutritional supplement for 4 weeks before TAVR with the addition of home-based supervised exercise sessions for 12 weeks after TAVR (intervention group). The primary outcome will be physical performance as measured by a blinded observer using the Short Physical Performance Battery at 3 months. Secondary outcomes at 3, 6, and 12 months will include HRQOL, as measured by the Short-Form 36 Physical and Mental Component summary scores, and a composite safety end point. The PERFORM-TAVR trial is testing a novel frailty intervention in older adults undergoing TAVR to optimise recovery and downstream HRQOL. This represents a potential paradigm shift that highlights the value of assessing and treating patients’ frailty in parallel with their underlying heart valve disease.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03522454.
En dépit du taux élevé de réussite remplacement valvulaire aortique par cathéter (RVAC), 2 personnes âgées sur 5 signalent une détérioration de leurs capacités physiques et de la qualité de vie liée à la santé dans les mois qui suivent l’intervention, particulièrement les patients fragiles. Aucun essai n’a encore été mené sur les effets synergiques de l’activité physique et de la supplémentation protéique pour contrer la fragilité et améliorer le devenir des patients après un RVAC. L’essai PERFORM-TAVR est un essai clinique multicentrique à répartition aléatoire mené avec groupes parallèles auquel participent 200 personnes fragiles âgées de 70 ans et plus qui subissent un RVAC. Les patients seront répartis aléatoirement dans l’un des deux groupes de traitements : éducation standard sur les habitudes de vie (groupe témoin) ou prise de supplément alimentaire riche en protéines par voie orale pendant 4 semaines avant le RVAC à laquelle s’ajoutent des séances d’exercices supervisées à domicile pendant 12 semaines après le RVAC (groupe d’intervention). Le principal critère d’évaluation sera la performance physique mesurée à l’insu par un observateur au moyen du SPPB (Short Physical Performance Battery) après 3 mois. Les critères d’évaluation secondaires à 3 mois, à 6 mois et à 12 mois comprendront la qualité de vie liée à la santé, mesurée par les scores sommaires des composantes physique et mentale du questionnaire SF-36 (Short-Form 36) et un paramètre composé de l’innocuité. L’essai PERFORM-TAVR vise à évaluer une nouvelle intervention en présence de fragilité chez les personnes âgées qui subissent un RVAC afin d’optimiser le rétablissement et la qualité de vie liée à la santé en aval. Cela représente un changement de paradigme possible qui met en lumière la valeur de l’évaluation et du traitement de la fragilité des patients en parallèle avec leur valvulopathie sous-jacente.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03522454.
Clinical frailty scale score during geriatric rehabilitation predicts short-term mortality: RESORT cohort study
2023, Annals of Physical and Rehabilitation Medicine
Citation Excerpt :
This observation should raise awareness among clinicians in attempting to improve or at least preserve individuals’ degree of frailty during hospitalisation. Additionally, multidomain interventions, many of which include an exercise component, have demonstrated promising results in improving frailty [33–35]. The timing of discharge was left to the discretion of the treating teams and negotiation, when appropriate, with individuals and/or families.
Frailty is associated with poor health outcomes, such as functional decline and institutionalization. The Clinical Frailty Scale (CFS) is a judgement-based frailty assessment tool developed to identify frail adults and assess level of frailty.
We aimed to determine the association between CFS at admission and discharge, admission-discharge change, and mortality in individuals admitted to geriatric rehabilitation.
REStORing health of acutely unwell adulTs (RESORT) is a longitudinal, observational inception cohort of consecutive individuals admitted to geriatric rehabilitation at the Royal Melbourne Hospital, Melbourne, Australia. The CFS was assessed at admission and discharge from geriatric rehabilitation. Logistic regression was used to examine the association between CFS score at admission and in-hospital mortality. Cox proportional hazards regression analysis was used to analyse associations between CFS at admission and discharge, admission-to-discharge change, and 3-month and 1-year mortality.
A total of 1766 participants were included: median age was 83.4 years (Interquartile range [IQR] 77.6–88.4), 57% were female, median length of stay in geriatric rehabilitation was 20 days (13.8–31.7) and median CFS score was 6 (5–7) at both admission and discharge. Increased CFS score was associated with in-hospital mortality (odds ratio [OR] 1.8, 95% CI 1.4–2.4), 3-month mortality and 1-year mortality (admission CFS: hazard ratio [HR] 1.4, 95% CI 1.2–1.6; discharge CFS: HR 1.4, 95% CI 1.2–1.7). Risk of 3-month mortality was increased when CFS score increased from admission to discharge (HR 2.1, 95% CI 1.2–3.8) as compared with when it decreased.
CFS score at admission and discharge was associated with post-discharge mortality in individuals admitted to geriatric rehabilitation. These findings support the use of the CFS in clinical settings to assist clinical characterisation and decision making.
Fatigue and the prediction of negative health outcomes: A systematic review with meta-analysis
2021, Ageing Research Reviews
Fatigue is a common complaint among older adults. Evidence grows that fatigue is linked to several negative health outcomes. A general overview of fatigue and its relationship with negative health outcomes still lacks in the existing literature. This brings complications for healthcare professionals and researchers to identify fatigue-related health risks. Therefore, this study gives an overview of the prospective predictive value of the main negative health outcomes for fatigue in community-dwelling older adults.
PubMed, Web of Knowledge and PsycINFO were systematically screened for prospective studies regarding the relationship between fatigue and negative health outcomes resulting in 4595 articles (last search 5th March 2020). Meta-analyses were conducted in RevMan using Odds ratios (ORs), Hazard ratios (HRs) and relative risk ratios (RR) that were extracted from the included studies. Subgroup-analyses were performed based on (1) gender (male/female), (2) length of follow-up and (3) fatigue level (low, medium and high).
In total, thirty articles were included for this systematic review and meta-analysis encompassing 152 711 participants (age range 40–98 years), providing information on the relationship between fatigue and health outcomes. The results showed that fatigue is related to an increased risk for the occurrence of all studied health outcomes (range OR 1.299–3.094; HR/RR 1.038–1.471); for example, mortality OR 2.14 [1.74–2.63]; HR/RR 1.44 [1.28–1.62]), the development of disabilities in basic activities of daily living (OR 3.22 [2.05–5.38]), or the occurrence of physical decline (OR 1.42 [1.29–1.57]).
Overall fatigue increases the risk for developing negative health outcomes. The analyses presented in this study show that fatigue related physical decline occurs earlier than hospitalization, diseases and mortality, suggesting the importance of early interventions.
The operationalization of fatigue in frailty scales: a systematic review
2019, Ageing Research Reviews
To identify the different fatigue items in existing frailty scales.
PubMed, Web of Knowledge and PsycINFO were systematically screened for frailty scales. 133 articles were included, describing 158 frailty scales. Fatigue items were extracted and categorized in 4 fatigue constructs: “mood state related tiredness”, “general feeling of tiredness”, “activity based feeling of tiredness” and “resistance to physical tiredness”.
120 fatigue items were identified, of which 100 belonged to the construct “general feeling of tiredness” and only 9 to the construct “resistance to physical tiredness”. 49,4% of the frailty scales included at least 1 fatigue item, representing 15 ± 9,3% of all items in these scales. Fatigue items have a significantly higher weight in single domain (dominantly physical frailty scales) versus multi domain frailty scales (21 ± 3.2 versus 10.6 ± 9.8%, p=<0,05).
Fatigue is prominently represented in frailty scales, covering a great diversity in fatigue constructs and underlying pathophysiological mechanisms by which fatigue relates to frailty. Although fatigue items were more prevalent and had a higher weight in physical frailty scales, the operationalization of fatigue leaned more towards psychological constructs. This review can be used as a reference for choosing a suitable frailty scale depending on the type of fatigue of interest.
Translating Frailty Research Into Clinical Practice: Insights From the Successful Aging and Frailty Evaluation Clinic
2019, Journal of the American Medical Directors Association
Citation Excerpt :
Our frailty risk reduction approach follows current evidence-based interventional studies that target a reduction in specific frailty syndrome criteria or that implement multifaceted interventions. Strategies have included targeted muscle strengthening with or without protein supplementation for identified weakness or slow gait and increasing exercise for people with low activity.20,21 We additionally address weight loss and exhaustion when present using targeted nutrition support and exploring factors that may be contributing to weight loss or exhaustion (eg, mood disorders, polypharmacy), but these interventions have not been as well studied in this context and remain controversial.20–22
Aging researchers have been studying frailty for decades. Experts agree that frailty is a medical syndrome marked by reduced physiologic function, which increases the risk of vulnerability and short-term mortality, particularly in the face of a stressor. Frailty has been shown to predict poor outcomes including falls, disability, major morbidity following surgery, and mortality among older adults. Despite hundreds of papers identifying frailty as a useful marker of risk, its translation into clinical practice has lagged. The Successful Aging and Frailty Evaluation (SAFE) clinic was established in 2011 specifically to implement routine and structured frailty assessment and management in a variety of referred patients. Now, more than 7 years after its inception, we offer our “in the trenches” clinical perspective on logistical challenges, the clinical utility of the frailty assessment, and future frailty needs and targets to help further the frailty translation research efforts.
Diabetes in Old Age
2023, Aktuelle Ernahrungsmedizin

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Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials

Abstract

Section snippets

Methods

Results

Discussion

Statement of Conflict of Interest

Lancet

Med Clin North Am

Clin Geriatr Med

Frailty assessment in the cardiovascular care of older adults

2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Frailty in older adults: evidence for a phenotype

J Gerontol A Biol Sci Med Sci

Cachexia versus sarcopenia

Physical activity as a preventative factor for frailty: the health, aging, and body composition study

J Gerontol A Biol Sci Med Sci

Systematic review of progressive resistance strength training in older adults

J Gerontol A Biol Sci Med Sci