Protocol for a randomised clinical trial of multimodal postconcussion symptom treatment and recovery: the Concussion Essentials study

IntroductionWhile most children recover from a concussion shortly after injury, approximately 30% experience persistent postconcussive symptoms (pPCS) beyond 1-month postinjury. Existing research into the treatment of pPCS have evaluated unimodal approaches, despite evidence suggesting that pPCS likely represent an interaction across various symptom clusters. The primary aim of this study is to evaluate the effectiveness of a multimodal, symptom-tailored intervention to accelerate symptom recovery and increase the proportion of children with resolved symptoms at 3 months postconcussion.Methods and analysisIn this open-label, assessor-blinded, randomised clinical trial, children with concussion aged 8–18 years will be recruited from The Royal Children’s Hospital (The RCH) emergency department, or referred by a clinician, within 17 days of initial injury. Based on parent ratings of their child’s PCS at ~10 days postinjury, symptomatic children (≥2 symptoms at least 1-point above those endorsed preinjury) will undergo a baseline assessment at 3 weeks postinjury and randomised into either Concussion Essentials (CE, n=108), a multimodal, interdisciplinary delivered, symptom-tailored treatment involving physiotherapy, psychology and education, or usual care (UC, n=108) study arms. CE participants will receive 1 hour of intervention each week, for up to 8 weeks or until pPCS resolve. A postprogramme assessment will be conducted at 3 months postinjury for all participants. Effectiveness of the CE intervention will be determined by the proportion of participants for whom pPCS have resolved at the postprogramme assessment (primary outcome) relative to the UC group. Secondary outcome analyses will examine whether children receiving CE are more likely to demonstrate resolution of pPCS, earlier return to normal activity, higher quality of life and a lower rate of utilisation of health services, compared with the UC group.Ethics and disseminationEthics were approved by The RCH Human Research Ethics Committee (HREC: 37100). Parent, and for mature minors, participant consent, will be obtained prior to commencement of the trial. Study results will be disseminated at international conferences and international peer-reviewed journals.Trial registration numberACTRN12617000418370; pre-results.

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Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) randomised clinical trial: study protocol

BMJ Open ◽

10.1136/bmjopen-2020-038300 ◽

2020 ◽

Vol 10 (5) ◽

pp. e038300

Author(s):

Nick Daneman ◽

Asgar H Rishu ◽

Ruxandra L Pinto ◽

Yaseen M Arabi ◽

Deborah J Cook ◽

...

Keyword(s):

Clinical Trial ◽

Antibiotic Treatment ◽

Treatment Duration ◽

Bloodstream Infections ◽

Clinical Effectiveness ◽

Randomised Clinical Trial ◽

Prosthetic Material ◽

Link Type ◽

Study Results ◽

Registration Number

IntroductionBloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied.Methods and analysisWe will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (Staphylococcus aureus, Staphylococcus lugdunensis, Candida and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms.Ethics and disseminationThe study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study results via the Canadian Critical Care Trials Group and other collaborating networks to set the global paradigm for antibiotic treatment duration for non-staphylococcal Gram-positive, Gram-negative and anaerobic bacteraemia, among patients admitted to hospital.Trial registration numberThe BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial was registered at www.clinicaltrials.gov (registration number: NCT03005145).

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Multicentre, randomised clinical trial of paediatric concussion assessment of rest and exertion (PedCARE): a study to determine when to resume physical activities following concussion in children

British Journal of Sports Medicine ◽

10.1136/bjsports-2017-097981 ◽

2017 ◽

Vol 53 (3) ◽

pp. 195-195 ◽

Cited By ~ 5

Author(s):

Andrée-Anne Ledoux ◽

Nicholas J Barrowman ◽

Kathy Boutis ◽

Adrienne Davis ◽

Sarah Reid ◽

...

Keyword(s):

Physical Activity ◽

Clinical Trial ◽

Randomised Clinical Trial ◽

Primary Objective ◽

Physical Activities ◽

Postconcussive Symptoms ◽

Intervention Protocol ◽

Registration Number ◽

Cognitive Activities ◽

Study Intervention

IntroductionRest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol.Methods and analysisThis study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total of 350 participants, aged 10–17.99 years, who present within 48 hours of an acute concussion, will be recruited and randomly assigned to either the study intervention protocol (resumption of physical activity 72 hours postconcussion even if experiencing symptoms) or physical rest until fully asymptomatic. Participants will document their daily physical and cognitive activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks postinjury. Compliance with the intervention will be measured using an accelerometer (24 hours/day for 14 days). Symptoms will be measured using the validated Health and Behaviour Inventory. A linear multivariable model, adjusting for site and prognostically important covariates, will be tested to determine differences between groups. The proposed protocol adheres to the RCT-CONSORT guidelines.DiscussionThis trial will determine if early resumption of non-contact physical activity following concussion reduces the burden of concussion and will provide healthcare professionals with the evidence by which to recommend the best timing of reintroducing physical activities.Trial registration numberTrial identifier (Clinicaltrials.gov) NCT02893969.

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Double-task exercise programmes to strengthen cognitive and vascular health in older adults at risk of cognitive decline: protocol for a randomised clinical trial

BMJ Open ◽

10.1136/bmjopen-2020-039723 ◽

2020 ◽

Vol 10 (12) ◽

pp. e039723

Author(s):

Rosalinda Sánchez-Arenas ◽

Svetlana V Doubova ◽

Mariela Bernabe-Garcia ◽

Michel A Gregory ◽

Laura Alejandra Mejía-Alonso ◽

...

Keyword(s):

Older Adults ◽

Clinical Trial ◽

At Risk ◽

Cognitive Decline ◽

Randomised Clinical Trial ◽

Outcome Variable ◽

Control Group ◽

Study Results ◽

Registration Number ◽

Exercise Programmes

IntroductionCognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs’ families. Programmes to prevent or delay OAs’ cognitive and physical decline are scarce.Methods and analysisA double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline—one programme with and another without caregiver participation—and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants’ demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima–media thickness; (6) OAs’ health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable.Ethics and disseminationThe study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community.Trial registration numberClinicalTrials.gov (NCT04068376).

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Staged angioplasty versus regular carotid artery stenting in patients with carotid artery stenosis at high risk of hyperperfusion: a randomised clinical trial

Stroke and Vascular Neurology ◽

10.1136/svn-2020-000391 ◽

2020 ◽

pp. svn-2020-000391

Author(s):

Dapeng Mo ◽

Baixue Jia ◽

Huaizhang Shi ◽

Yaxuan Sun ◽

Qingan Liu ◽

...

Keyword(s):

Clinical Trial ◽

High Risk ◽

Carotid Artery ◽

Primary Endpoint ◽

Carotid Artery Stenting ◽

Absolute Risk ◽

Absolute Risk Reduction ◽

Randomised Clinical Trial ◽

Open Label ◽

Registration Number

Background and purposeHyperperfusion (HP) is a devastating complication associated with carotid artery stenting (CAS) or endarterectomy. The efficacy and safety of staged angioplasty (SAP) in patients with CAS at high risk of HP remains unclear. We sought to determine whether SAP is superior to regular CAS in patients with high risk of HP.MethodsA randomised, multicentre open-label clinical trial with blinded outcome assessment (STEP) was conducted. Patients with severe carotid stenosis at high risk of HP were randomly assigned (1:1) to the SAP or regular CAS group. The primary endpoint was hyperperfusion syndrome (HPS) and intracerebral haemorrhage (ICH) within 30 days after the procedure.ResultsFrom November 2014 to January 2017, a total of 64 patients were enrolled in 11 centres. 33 patients were allocated to the SAP group and 31 to the regular CAS group. At 30 days, the rate of primary endpoint was 0.0% (0/33) in the SAP group and 9.7% (3/31) in the regular CAS group (absolute risk reduction (ARR), 9.7%; 95% CI −20.1% to 0.7%; p=0.11). As one of the secondary endpoints, the incidence of HP phenomenon (HPP) was lower in the SAP group than the regular CAS group (0.0% vs 22.6%, ARR,−22.6%; 95% CI −36.8% to −10.2%; p=0.04).ConclusionThe rate of HPS and ICH was not significantly lower in SAP group; the extended secondary endpoint of HPP, however, significantly reduced, which suggested that SAP may be a safe and effective carotid revascularisation procedure to prevent HP.Trial registration numberNCT02224209.

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COpenhagen Neuroplastic TRaining Against Contractures in Toddlers (CONTRACT): protocol of an open-label randomised clinical trial with blinded assessment for prevention of contractures in infants with high risk of cerebral palsy

BMJ Open ◽

10.1136/bmjopen-2020-044674 ◽

2021 ◽

Vol 11 (7) ◽

pp. e044674

Author(s):

Maria Willerslev-Olsen ◽

Jakob Lorentzen ◽

Katrine Røhder ◽

Anina Ritterband-Rosenbaum ◽

Mikkel Justiniano ◽

...

Keyword(s):

Clinical Trial ◽

Cerebral Palsy ◽

High Risk ◽

Standard Care ◽

Muscle Growth ◽

Randomised Clinical Trial ◽

Triceps Surae ◽

Secondary Outcome ◽

Secondary Outcome Measure ◽

Open Label

IntroductionContractures are frequent causes of reduced mobility in children with cerebral palsy (CP) already at the age of 2–3 years. Reduced muscle use and muscle growth have been suggested as key factors in the development of contractures, suggesting that effective early prevention may have to involve stimuli that can facilitate muscle growth before the age of 1 year. The present study protocol was developed to assess the effectiveness of an early multicomponent intervention, CONTRACT, involving family-oriented and supervised home-based training, diet and electrical muscle stimulation directed at facilitating muscle growth and thus reduce the risk of contractures in children at high risk of CP compared with standard care.Methods and analysisA two-group, parallel, open-label randomised clinical trial with blinded assessment (n=50) will be conducted. Infants diagnosed with CP or designated at high risk of CP based on abnormal neuroimaging or absent fidgety movement determined as part of General Movement Assessment, age 9–17 weeks corrected age (CA) will be recruited. A balanced 1:1 randomisation will be made by a computer. The intervention will last for 6 months aiming to support parents in providing daily individualised, goal-directed activities and primarily in lower legs that may stimulate their child to move more and increase muscle growth. Guidance and education of the parents regarding the nutritional benefits of docosahexaenic acid (DHA) and vitamin D for the developing brain and muscle growth will be provided. Infants will receive DHA drops as nutritional supplements and neuromuscular stimulation to facilitate muscle growth. The control group will receive standard care as offered by their local hospital or community. Outcome measures will be taken at 9, 12, 18, 24, 36 and 48 months CA. Primary and secondary outcome measure will be lower leg muscle volume and stiffness of the triceps surae musculotendinous unit together with infant motor profile, respectively.Ethics and disseminationFull approval from the local ethics committee, Danish Committee System on Health Research Ethics, Region H (H-19041562). Experimental procedures conform with the Declaration of Helsinki.Trial registration numberNCT04250454.Expected recruitment period1 January 2021–1 January 2025.

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Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial

Open Heart ◽

10.1136/openhrt-2021-001614 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001614

Author(s):

Mohammad R Ostovaneh ◽

Raj R Makkar ◽

Bharath Ambale-Venkatesh ◽

Deborah Ascheim ◽

Tarun Chakravarty ◽

...

Keyword(s):

Myocardial Infarction ◽

Clinical Trial ◽

Myocardial Function ◽

Randomised Clinical Trial ◽

Scar Tissue ◽

Left Ventricular ◽

Lv Function ◽

Cardiac Events ◽

Lv Dysfunction ◽

Registration Number

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups.ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

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Open-label placebo for insomnia (OPIN): study protocol for a cohort multiple randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-044045 ◽

2021 ◽

Vol 11 (2) ◽

pp. e044045

Author(s):

Ben Colagiuri ◽

Louise Sharpe ◽

Zahava Ambarchi ◽

Nick Glozier ◽

Delwyn Bartlett ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Treatment Period ◽

Controlled Trial ◽

Severity Index ◽

Open Label ◽

Human Research Ethics ◽

Sleep Parameters ◽

Registration Number ◽

Randomised Controlled ◽

Insomnia Symptoms

IntroductionInsomnia is a prevalent sleep disorder that causes substantial personal and societal harm. There is evidence that placebo interventions can reduce insomnia symptoms, but this research has involved deceptively administering the placebo under the guise of a real medication (conventional placebo, CP), which has obvious ethical constraints. Open-label placebo (OLP) treatment, in which a placebo is administered with full disclosure that there are no active ingredients, has been proposed as a method of using the placebo effect ethically, but the efficacy and acceptability of OLP for insomnia is currently unknown.Methods and analysisThis study uses a cohort multiple randomised controlled trial design to compare OLP, CP and no treatment for insomnia. Two-hundred and sixty-seven participants with self-reported insomnia symptoms (Insomnia Severity Index, ISI ≥10) will be recruited into an observational study and have their sleep monitored over a 2-week period. Participants will then be randomised to one of three groups: invite to OLP, invite to CP described deceptively as a new pharmacological agent, or no invite/observational control. Those in OLP and CP accepting the invite receive identical placebos for a 2-week treatment period while sleep is monitored in all participants. The primary outcome is ISI at the end of the treatment period. Secondary outcomes include treatment uptake and clinically significant response rates, objective and subjective sleep parameters, fatigue, mood, expectancy, treatment satisfaction and side effects. Predictors of uptake and responses to OLP and CP will be explored.Ethics and disseminationThe trial has been approved by The University of Sydney Human Research Ethics Committee. Written informed consent is obtained from every participant. OLP and CP participants accepting the invite undergo an additional consent process. Results will be disseminated via peer-reviewed conference proceedings and publications.Trial registration numberACTRN12620001080910.

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Adjustable intragastric balloon for treatment of obesity: a multicentre, open-label, randomised clinical trial

The Lancet ◽

10.1016/s0140-6736(21)02394-1 ◽

2021 ◽

Author(s):

Barham K Abu Dayyeh ◽

Daniel B Maselli ◽

Babusai Rapaka ◽

Thomas Lavin ◽

Mark Noar ◽

...

Keyword(s):

Clinical Trial ◽

Intragastric Balloon ◽

Randomised Clinical Trial ◽

Open Label ◽

Treatment Of Obesity

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Effects of home-based mirror therapy and cognitive therapeutic exercise on the improvement of the upper extremity functions in patients with severe hemiparesis after a stroke: a protocol for a pilot randomised clinical trial

BMJ Open ◽

10.1136/bmjopen-2019-035768 ◽

2020 ◽

Vol 10 (9) ◽

pp. e035768

Author(s):

Josefa Gonzalez-Santos ◽

Raul Soto-Camara ◽

Paula Rodriguez-Fernández ◽

Maria Jimenez-Barrios ◽

Jeronimo Gonzalez-Bernal ◽

...

Keyword(s):

Clinical Trial ◽

Upper Extremity ◽

Randomised Clinical Trial ◽

Therapeutic Exercise ◽

Mirror Therapy ◽

Link Type ◽

Home Based ◽

Study Results ◽

Task Oriented

IntroductionNeuroplasticity is defined as the capacity of the brain to reorganise new neuronal pathways. Mirror therapy (MT) and cognitive therapeutic exercise (CTE) are two neurorehabilitation techniques based on neuroplasticity and designed to improve the motor functions of the affected upper extremity in patients with severe hemiparesis after a stroke. Home-based interventions are an appropriate alternative to promote independence and autonomy. The objective of this study is to evaluate which of these techniques, MT and CTE, combined with task-oriented training, is more effective in functional recovery and movement patterns of the upper extremities in patients with severe hemiparesis after a stroke.Methods and analysisThis is a home-based, single-blind, controlled, randomised clinical trial with three parallel arms, including 154 patients who had a stroke aged above 18 years. The primary outcome will be the functionality of the affected upper extremity measured using the Fugl-Meyer Assessment. Secondary variables will include cognitive performance, emotional state, quality of life and activities of daily living. During 6 weeks, one of the intervention groups will receive a treatment based on MT and the other one on CTE, both combined with task-oriented training. No additional interventions will be provided to the control group. To assess the progress of patients who had a stroke in the subacute phase, all variables will be evaluated at different visits: initial (just before starting treatment and 4 weeks post-stroke), post-intervention (6 weeks after initial) and follow-up (6 months).Ethics and disseminationThis protocol has been approved by the Institutional Review Board (CEIm-2.134/2.019) and registered at ClinicalTrials.gov (NCT04163666). The results will be disseminated through open-access peer-reviewed journals, conference presentation, broadcast media and a presentation to stakeholders. These study results will provide relevant and novel information on effective neurorehabilitation strategies and improve the quality of intervention programmes aimed at patients after a stroke.Trial registration numberClinicalTrials.gov (NCT04163666).

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