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Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).

ABSTRACT: INTRODUCTION:Shoulder pain is very common, with around 70% of cases due to disorders of the rotator cuff. Despite widespread provision of physiotherapy, there is uncertainty about which type of exercise and delivery mechanisms are associated with best outcomes. There is also uncertainty around the long-term benefits and harms of corticosteroid injection therapy, which is often used in addition to physiotherapy. The Getting it Right: Addressing Shoulder Pain trial will assess the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS AND ANALYSIS:We are conducting a large multicentre randomised controlled trial (2×2 factorial design). We will recruit adults ?18 years with a new episode of shoulder pain attributable to a rotator cuff disorder as per British Elbow and Shoulder Society guidelines, not currently receiving physiotherapy or being considered for surgery, from at least eight UK National Health Service primary care-based musculoskeletal and related physiotherapy services. Participants (n=704) will be randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (?6 physiotherapy sessions); (2) best practice advice (one physiotherapy session); (3) corticosteroid injection then progressive exercise (?6 sessions) or (4) corticosteroid injection then best practice advice (one session). The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score at 12 months. Secondary outcomes are: pain and function SPADI subdomains; health-related quality of life (Five-Level version of the EuroQol EQ-5D-5L); sleep disturbance; return to activity; global impression of change; health resource use; out-of-pocket expenses; work disability. A parallel within-trial economic evaluation will be conducted. The primary analysis will be intention to treat. ETHICS AND DISSEMINATION:Research Ethics Committee approval (REC: 16/SC/0508) has been obtained. Results of the main trial and secondary outcomes will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:ISRCTN16539266; EudraCT number: 2016-002991-28.

SUBMITTER: Hopewell S

PROVIDER: S-EPMC5683303 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).

Hopewell Sally S Keene David J DJ Maia Schlüssel Michael M Dritsaki Melina M Dutton Susan S Carr Andrew A Hamilton William W Hansen Zara Z Jaggi Anju A Littlewood Chris C Soutakbar Hessam H Heine Peter P Cureton Lucy L Barker Karen K Lamb Sarah E SE

BMJ open 20170717 7

<h4>Introduction</h4>Shoulder pain is very common, with around 70% of cases due to disorders of the rotator cuff. Despite widespread provision of physiotherapy, there is uncertainty about which type of exercise and delivery mechanisms are associated with best outcomes. There is also uncertainty around the long-term benefits and harms of corticosteroid injection therapy, which is often used in addition to physiotherapy. The Getting it Right: Addressing Shoulder Pain trial will assess the clinical ...[more]

PMID: 28716796

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Project description:BackgroundCorticosteroid injections and physiotherapy exercise programmes are commonly used to treat rotator cuff disorders but the treatments' effectiveness is uncertain. We aimed to compare the clinical effectiveness and cost-effectiveness of a progressive exercise programme with a single session of best practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder.MethodsIn this pragmatic, multicentre, superiority, randomised controlled trial (2 × 2 factorial), we recruited patients from 20 UK National Health Service trusts. We included patients aged 18 years or older with a rotator cuff disorder (new episode within the past 6 months). Patients were excluded if they had a history of significant shoulder trauma (eg, dislocation, fracture, or full-thickness tear requiring surgery), neurological disease affecting the shoulder, other shoulder conditions (eg, inflammatory arthritis, frozen shoulder, or glenohumeral joint instability), received corticosteroid injection or physiotherapy for shoulder pain in the past 6 months, or were being considered for surgery. Patients were randomly assigned (centralised computer-generated system, 1:1:1:1) to progressive exercise (≤6 sessions), best practice advice (one session), corticosteroid injection then progressive exercise, or corticosteroid injection then best practice advice. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score over 12 months, analysed on an intention-to-treat basis (statistical significance set at 1%). The trial was registered with the International Standard Randomised Controlled Trial Register, ISRCTN16539266, and EuDRACT, 2016-002991-28.FindingsBetween March 10, 2017, and May 2, 2019, we screened 2287 patients. 708 patients were randomly assigned to progressive exercise (n=174), best practice advice (n=174), corticosteroid injection then progressive exercise (n=182), or corticosteroid injection then best practice advice (n=178). Over 12 months, SPADI data were available for 166 (95%) patients in the progressive exercise group, 164 (94%) in the best practice advice group, 177 (97%) in the corticosteroid injection then progressive exercise group, and 175 (98%) in the corticosteroid injection then best practice advice group. We found no evidence of a difference in SPADI score between progressive exercise and best practice advice when analysed over 12 months (adjusted mean difference -0·66 [99% CI -4·52 to 3·20]). We also found no evidence of a difference between corticosteroid injection compared with no injection when analysed over 12 months (-1·11 [-4·47 to 2·26]). No serious adverse events were reported.InterpretationProgressive exercise was not superior to a best practice advice session with a physiotherapist in improving shoulder pain and function. Subacromial corticosteroid injection provided no long-term benefit in patients with rotator cuff disorders.FundingUK National Institute for Health Research Technology Assessment Programme.

Project description:BackgroundThe Getting it Right: Addressing Shoulder Pain (GRASP) trial assesses the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. This article describes the statistical analysis plan for the GRASP randomised controlled trial.Methods/designGRASP is a multicentre randomised controlled trial using a 2 × 2 factorial design. Adults aged ≥ 18 years with a new episode of shoulder pain related to a rotator cuff disorder, not currently receiving physiotherapy or being considered for surgery, are randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (up to 6 physiotherapy sessions), (2) best practice advice (one physiotherapy session), (3) subacromial corticosteroid injection then progressive exercise and (4) subacromial corticosteroid injection then best practice advice. The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score over 12 months. Secondary outcomes are as follows: pain and function SPADI subdomains, health-related quality of life (EuroQol EQ-5D-5L), sleep disturbance, return to activity, global impression of change, health resource use, out-of-pocket expenses and work disability. Here, we describe in detail the following: sample size calculation, descriptive statistics of the primary and secondary outcomes, statistical models used for the analysis of the main outcomes, handling of missing data, planned sensitivity and subgroup analyses. This pre-specified statistical analysis plan was written and submitted without prior knowledge of the trial results.DiscussionPublication of the statistical analysis plan for the GRASP trial aims to reduce the risk of outcome reporting bias and increase transparency of the data analysis. Any deviations or changes to the current SAP will be described and justified in the final study report and any results publications.Trial registrationInternational Standard Randomised Controlled Trial Number ISRCTN16539266 . Registered on 14 June 2016. EudraCT number 2016-002991-28. Registered on 12 June 2016.

Project description:Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis.

Project description:Importance:Rotator cuff disorders remain the most common cause of shoulder pain and are among the most common reasons for patients to seek care in primary and specialty settings. Although operative and nonoperative treatments are offered to patients with atraumatic rotator cuff tears, there is a lack of evidence to support operative vs nonoperative treatment. This paucity of evidence has been highlighted by several professional agencies and experts. Objective:To perform a pragmatic randomized clinical trial, the Arthroscopic Rotator Cuff trial, comparing pain and functional outcomes in patients undergoing operative vs nonoperative treatment for atraumatic rotator cuff tears, and assessing heterogeneity of treatment effects by age and tear size. Design, Setting, and Participants:Trial protocol of the Arthroscopic Rotator Cuff trial. This pragmatic randomized clinical trial of an estimated 700 patients is adequately powered to accomplish its aims with 488 patients. Primary analysis will be conducted on an intent-to-treat population in the context of a mixed model. The multicenter trial started recruitment in 2018 with a 1-year follow-up duration. Patients aged 50 years or older to younger than 85 years with magnetic resonance imaging-confirmed atraumatic rotator cuff tears that are suitable for either operative or nonoperative treatment will be enrolled. Block randomization will be performed and stratified by site, age, and tear size. Intervention:Nonoperative treatment consists of an approximately 3-month standardized physical therapy program, whereas operative treatment consists of rotator cuff surgery followed by approximately 4 months of postoperative rehabilitation. Main Outcomes and Measures:The primary outcome is patient-reported Shoulder Pain and Disability Index score, and the secondary outcome is American Shoulder and Elbow Surgeons Standardized Shoulder Form score measured at 1 year of follow-up. Discussion:The Arthroscopic Rotator Cuff trial is ongoing, and 12 sites with more than 40 physicians are currently recruiting patients. Although there is variation by site, as of May 2, 2019, 13% of all patients screened (787 of 6293) were eligible for the trial, and 9% of eligible patients (74 of 787) were recruited. Results of this study may help patients, clinicians, and policy makers assess the comparative effectiveness of operative vs nonoperative treatment for atraumatic rotator cuff tears. Trial Registration:ClinicalTrials.gov identifier: NCT03295994.

Project description:Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016.

Project description:BackgroundThe ability of injection of corticosteroids into the subacromial space to relieve pain ascribed to rotator cuff tendinosis is debated. The number of patients who have an injection before one gets relief beyond what a placebo provides is uncertain.Questions/purposesWe asked: (1) Do corticosteroid injections reduce pain in patients with rotator cuff tendinosis 3 months after injection, and if so, what is the number needed to treat (NNT)? (2) Are multiple injections better than one single injection with respect to pain reduction at 3 months?MethodsWe systematically searched seven electronic databases for randomized controlled trials of corticosteroid injection for rotator cuff tendinosis compared with a placebo injection. Eligible studies had at least 10 adults and used pain intensity as an outcome measure. The Hedges's g as adjusted pooled standardized mean difference (SMD) (which expresses the size of the intervention effect in each study relative to the total variability observed among pooled studies) and NNT were calculated at assessment points less than 1 month, 1-2 months, and 2-3 months. The protocol of this study was registered at the international prospective register of systematic reviews. Eleven studies of 726 patients satisfied our criteria for data pooling. Three studies containing 292 patients used repeat injections. A random effects model was used owing to substantial heterogeneity among studies. The funnel plot indicated the possibility of some missing studies, but Orwin's fail-safe N and Duval and Tweedie's trim and fill suggested that missing studies would not significantly affect the results.ResultsCorticosteroid injection did not reduce pain intensity in adult patients with rotator cuff tendinosis more than a placebo injection at the 3-month assessment. A small transient pain relief occurred at the assessment between 4 and 8 weeks with a SMD of 0.52 (range, 0.27-0.78) (p < 0.001). At least five patients must be treated for one patient's pain to be transiently reduced to no more than mild. Multiple injections were not found to be more effective than a single injection at any time.ConclusionsCorticosteroid injections provide-at best-minimal transient pain relief in a small number of patients with rotator cuff tendinosis and cannot modify the natural course of the disease. Given the discomfort, cost, and potential to accelerate tendon degeneration associated with corticosteroids, they have limited appeal. Their wide use may be attributable to habit, underappreciation of the placebo effect, incentive to satisfy rather than discuss a patient's drive toward physical intervention, or for remuneration, rather than their utility.Level of evidenceLevel I, therapeutic study.

Project description:BACKGROUND:Rotator cuff tear is a common cause of shoulder disability and results in patients predominantly complaining of pain and loss of motion and strength. Traumatic rotator cuff tears are typically managed surgically followed by ~?20 weeks of rehabilitation. However, the timing and intensity of the postoperative rehabilitation strategy required to reach an optimal clinical outcome is unknown. Early controlled and gradually increased tendon loading has been suggested to positively influence tendon healing and recovery. The aim of this trial is therefore to examine the effect of a progressive rehabilitation strategy on pain, physical function and quality of life compared to usual care (that limits tendon loading in the early postoperative phase) in patients who have a rotator cuff repair of a traumatic tear. METHODS:The current study is a randomized, controlled, outcome-assessor blinded, multicenter, superiority trial with a two-group paralleled design. A total of 100 patients with surgically repaired traumatic rotator cuff tears will be recruited from up to three orthopedic departments in Denmark, and randomized to either a progressive early passive and active movement program or a limited early passive movement program (usual care). The primary outcome measure will be the change from pre-surgery to 12 weeks post-surgery in the Western Ontario Rotator Cuff Index questionnaire. Secondary outcomes include the Disabilities Arm, Shoulder and Hand questionnaire (DASH), range of motion, strength and tendon healing characteristics from ultrasound measurements at 12 months follow up. DISCUSSION:We hypothesized that patients who receive the progressive rehabilitation strategy will benefit more with respect to pain reduction, physical function and quality of life than those who receive care as usual. If this is confirmed our study can be used clinically to enhance the recovery of patients with traumatic rotator cuff tear. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02969135 . Registered on 15 November 2016.

Dataset Information

Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).

Publications

Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).

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