-
Trials Dec 2023Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence...
Effectiveness of full Pulpotomy compared with Root canal treatment in managing teeth with signs and symptOms indicative of irreversible pulpitis: a protocol for prospectiVE meta-analysis of individual participant data of linked randomised clinical trials (PROVE).
BACKGROUND
Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence is limited, relying on underpowered studies with a high risk of bias. The aim of this study is to conduct a prospective meta-analysis (PMA) of individual participant data of a series of individual randomised trials to provide robust evidence on the clinical and cost-effectiveness of pulpotomy compared with root canal treatment.
METHODS
Individual participant data will be obtained from a series of randomised trials designed and conducted by a consortium of multi-national investigators with an interest in vital pulp treatment. These individualised trials will be conducted using a specified protocol, defined outcomes, and outcome measures. Ten parallel-group randomised trials currently being conducted in 10 countries will provide data from more than 500 participants. The primary outcome is a composite measure defined as (1) the absence of pain indicative of IRP, (2) the absence of signs and symptoms indicative of acute or chronic apical periodontitis, and (3) the absence of radiographic evidence of failure including radiolucency or resorption. Individual participant data will be obtained, assessed, and checked for quality by two independent reviewers prior to the PMA. Pooled estimates on treatment effects will be generated using a 2-stage meta-analysis approach. The first stage involves a standard regression analysis in each trial to produce aggregate data on treatment effect estimates followed by an inverse variance weighted meta-analysis to combine these aggregate data and produce summary statistics and forest plots. Cost-effectiveness analysis based on the composite outcome will be undertaken as a process evaluation to evaluate treatment fidelity and acceptability by patients and dentists.
RESULTS
The research question and trial protocol were developed and approved by investigators in all 10 sites. All sites use shared resources including study protocols, data collection forms, participant information leaflets, and consent forms in order to improve flow, consistency, and reproducibility. Each site obtained its own Institutional Review Board approval, and trials were registered in appropriate open access platforms. Patient recruitment has started in most sites, as of July 2023.
DISCUSSION
PMA offers a rigorous, flexible, and efficient methodology to answer this important research question and provide results with improved generalisability and external validity compared with traditional trials and retrospective meta-analyses. The results of this study will have implications for both the delivery of clinical practice and structured clinical guidelines' development.
TRIAL REGISTRATION
PROSPERO CRD42023446809. Registered on 08 February 2023.
Topics: Humans; Dental Pulp Cavity; Meta-Analysis as Topic; Prospective Studies; Pulpitis; Pulpotomy; Randomized Controlled Trials as Topic; Reproducibility of Results; Retrospective Studies; Treatment Outcome
PubMed: 38102685
DOI: 10.1186/s13063-023-07836-6 -
BMC Cardiovascular Disorders Aug 2023To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive...
Comparison of two diagnostic strategies for patients with stable chest pain suggestive of chronic coronary syndrome: rationale and design of the double-blind, pragmatic, randomized and controlled OPERATE Trial.
BACKGROUND
To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive minimal benefit from further cardiac imaging testing (CIT) is important for patients with stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS). Although several diagnostic strategies have been recommended by the most recent guidelines, few randomized controlled trials (RCTs) have prospectively investigated the actual effect of applying these strategies in clinical practice.
METHODS
OPERATE (OPtimal Evaluation of stable chest pain to Reduce unnecessAry utilization of cardiac imaging TEsting) trial is an investigator-initiated, multicenter, coronary computed tomography angiography (CCTA)-based, 2-arm parallel-group, double-blind, pragmatic and confirmative RCT planning to include 800 subjects with SCP suggestive of CCS. After enrollment, all subjects will be randomized to two arms (2016 U.K. National Institute of Health and Care Excellence guideline-determined and 2019 European Society of Cardiology guideline-determined diagnostic strategy) on a 1:1 basis. According to each strategy, CCTA should be referred and deferred for a subject in high and low risk group, respectively. The primary (effectiveness) endpoint is CCTA without obstructive coronary artery disease. Safety of each strategy will be mainly assessed by 1-year major adverse cardiovascular event rates.
DISCUSSION
The OPERATE trial will provide comparative effectiveness and safety evidences for two different diagnostic strategies for patients with SCP suggestive of CCS, with the intension of improving the diagnostic yield of CCTA at no expense of safety.
CLINICAL TRIAL REGISTRATION
ClinicalTrial.org Identifier NCT05640752.
Topics: Humans; Heart; Chest Pain; Coronary Artery Disease; Patients; Computed Tomography Angiography; Syndrome; Randomized Controlled Trials as Topic
PubMed: 37612631
DOI: 10.1186/s12872-023-03424-3 -
Pediatric Neurology Aug 2023The field of pediatric skeletal muscle channelopathies has seen major new advances in terms of a wider understanding of clinical presentations and new phenotypes.... (Review)
Review
The field of pediatric skeletal muscle channelopathies has seen major new advances in terms of a wider understanding of clinical presentations and new phenotypes. Skeletal muscle channelopathies cause significant disability and even death in some of the newly described phenotypes. Despite this, there are virtually no data on the epidemiology and longitudinal natural history of these conditions or randomized controlled trial evidence of efficacy or tolerability of any treatment in children, and thus best practice care recommendations do not exist. Clinical history, and to a lesser extent examination, is key to eliciting symptoms and signs that indicate a differential diagnosis of muscle channelopathy. Normal routine investigations should not deter one from the diagnosis. Specialist neurophysiologic investigations have an additional role, but their availability should not delay genetic testing. New phenotypes are increasingly likely to be identified by next-generation sequencing panels. Many treatments or interventions for symptomatic patients are available, with anecdotal data to support their benefit, but we lack trial data on efficacy, safety, or superiority. This lack of trial data in turn can lead to hesitancy in prescribing among doctors or in accepting medication by parents. Holistic management addressing work, education, activity, and additional symptoms of pain and fatigue provides significant benefit. Preventable morbidity and sometimes mortality occurs if the diagnosis and therefore treatment is delayed. Advances in genetic sequencing technology and greater access to testing may help to refine recently identified phenotypes, including histology, as more cases are described. Randomized controlled treatment trials are required to inform best practice care recommendations. A holistic approach to management is essential and should not be overlooked. Good quality data on prevalence, health burden, and optimal treatment are urgently needed.
Topics: Child; Humans; Channelopathies; Muscle, Skeletal; Genetic Testing; Randomized Controlled Trials as Topic
PubMed: 37315339
DOI: 10.1016/j.pediatrneurol.2023.05.012 -
Clinical Cardiology Jan 2024Pulmonary arterial hypertension (PAH) is a widespread condition that affects around 1% of the global population, with a higher prevalence among older individuals. The... (Meta-Analysis)
Meta-Analysis Review
Pulmonary arterial hypertension (PAH) is a widespread condition that affects around 1% of the global population, with a higher prevalence among older individuals. The approach to managing PAH has undergone significant changes, requiring extensive treatment strategies. Sotatercept, an FDA-approved medication, has recently attracted attention for its potential role in PAH therapy. However, information on its safety and effectiveness is scarce. In this study, we performed a meta-analysis of existing randomized clinical trials to assess the impact of Sotatercept on PAH patients. Our findings revealed that those treated with Sotatercept showed greater improvement in pulmonary vascular resistance and World Health Organization functional class compared with placebo recipients. The occurrence of adverse events was similar between both groups. Importantly, the Sotatercept group displayed a considerably higher number of cases with an increase in hemoglobin levels. Considering that about 33% of PAH patients experience anemia and both anemia and polycythemia can adversely affect disease prognosis, additional research is necessary to establish the potential advantages and disadvantages of Sotatercept as a treatment choice, specifically regarding its erythropoietic properties.
Topics: Humans; Anemia; Prognosis; Pulmonary Arterial Hypertension; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins
PubMed: 37819149
DOI: 10.1002/clc.24173 -
Trials Oct 2023Myopia prevalence has been increasing in the last decades, and its pathological consequences, including myopic maculopathy and high myopia-associated optic neuropathy,...
BACKGROUND
Myopia prevalence has been increasing in the last decades, and its pathological consequences, including myopic maculopathy and high myopia-associated optic neuropathy, are now one of the most common causes of visual impairment. It is estimated that by 2050, more than 50% of Europeans and Americans will be myopes, which is alarming due to the high morbidity of myopes over - 6.00D. Once myopia has appeared, there are different options with scientific evidence to try to slow the axial length growth. Ophthalmic lenses are the less invasive treatment to control myopia, and there is evidence about the efficacy of different designs, mainly in the Asiatic population. However, new designs have been launched, and it is not known if efficacy is the same between Asiatic and European subjects. Thus, we have set up a randomized, controlled, double-blind, and multicenter trial to investigate the efficacy of a new design of ophthalmic lenses for myopia control in European children.
METHODS
A 2-year prospective, multicenter, randomized controlled, and double-blind clinical trial is used to investigate the efficacy of a new design of ophthalmic lenses to slow the progression of myopia. Three hundred children aged from 6 to 13 years old will be recruited and randomly assigned to a study or control group. The study group will be composed of 150 children wearing MyoCare while the control group will be composed of 150 children wearing Clearview. The inclusion criteria will be myopia with a spherical equivalent between - 0.75D and - 5.00D, astigmatism < 1.50D, and anisometropia < 1.00D and having a historical evolution of at least - 0.50 The primary outcome is to compare the mean annual progression of the spherical equivalent between both groups. The secondary outcomes are axial length, choroidal thickness, phorias, and accommodative status of both groups.
DISCUSSION
This study will be the first randomized and controlled clinical trial in European children with spectacle lenses based on simultaneous competing defocus. The results will shed light on the clinical evidence of spectacle lenses relying on this new design for the management of myopia with results of efficacy in the non-Asiatic population.
TRIAL REGISTRATION
EU Clinical Trials Register (EudraCT) 2022-001696. Registered on 27 April 2022.
CLINICALTRIALS
gov NCT05919654. Registered on 26 June 2023.
Topics: Child; Humans; Adolescent; Prospective Studies; Myopia; Refraction, Ocular; Double-Blind Method; Disease Progression; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37848908
DOI: 10.1186/s13063-023-07696-0 -
Trials Aug 2023Scapholunate advanced collapse (SLAC) and scaphoid non-union advanced collapse (SNAC) are common types of wrist osteoarthritis (OA). Non-operative treatment consists of...
Proximal ROw carpectOmy versus four-corner Fusion (PROOF-trial) for osteoarthritis of the wrist: study protocol for multi-institutional double-blinded randomized controlled trial.
BACKGROUND
Scapholunate advanced collapse (SLAC) and scaphoid non-union advanced collapse (SNAC) are common types of wrist osteoarthritis (OA). Non-operative treatment consists of pain medication, splinting, and avoiding activities that induce pain. However, in case a course of conservative treatment is unsuccessful, operative treatment is needed. The two most conventional operative approaches for SLAC/SNAC OA are four-corner arthrodesis (FCA) and proximal row carpectomy (PRC). Although FCA is the gold-standard operative technique and may lead to superior grip strength, the evident benefit of PRC is that it obviates any need for hardware removal and controlling for bony union. To date, no high-quality randomized controlled trial comparing FCA and PRC exists. As clinical outcomes seem comparable, a trial that assesses patient-reported outcomes, adverse events, and secondary operations may guide clinical decision making between these two procedures. Thus, the aim of this multi-institutional double-blind randomized controlled trial is to study whether PRC is non-inferior to FCA in treating SLAC/SNAC OA. We hypothesize that PRC is non-inferior to FCA with lower economic expanses.
METHODS
The trial is designed as a randomized, controlled, patient- and outcome-assessor blinded multicenter, two-armed 1:1 non-inferiority trial. Patients with SLAC/SNAC-induced wrist pain meeting trial inclusion criteria will undergo wrist arthroscopy to further assess eligibility. Each patient eligible for the trial will be randomly assigned to undergo either FCA or PRC. The primary endpoint of this study is the Patient Rated Wrist Evaluation (PRWE) at 1-year after FCA versus PRC. Secondary outcomes include Quick-Disabilities of the Arm, Shoulder and Hand, EQ-5D-5L, pain, grip strength, wrist active range of motion, radiographic evaluation, and adverse events. Trial design, methods, and statistical analysis plan will be presented here.
DISCUSSION
We present an RCT design comparing FCA vs PRC for SLAC/SNAC-induced OA. The results of this trial will assist in decision making when planning surgery for SLAC/SNAC.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04260165 . Registered February 7, 2020.
Topics: Humans; Wrist; Scaphoid Bone; Wrist Joint; Osteoarthritis; Arthrodesis; Pain; Range of Motion, Articular; Hand Strength; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37550711
DOI: 10.1186/s13063-023-07544-1 -
Neurocritical Care Apr 2024Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to...
Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a "worst-case" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.
Topics: Adult; Humans; Brain Edema; Neuroinflammatory Diseases; Cerebral Hemorrhage; Edema; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase II as Topic; Piperazines; Pyridazines; Pyridines
PubMed: 37919545
DOI: 10.1007/s12028-023-01867-2 -
BMC Neurology Oct 2023Chronic cluster headache (CCH) is a debilitating primary headache disorder. Occipital nerve stimulation (ONS) has shown the potential to reduce attack frequency, but the...
The HortONS study. Treatment of chronic cluster headache with transcutaneous electrical nerve stimulation and occipital nerve stimulation: study protocol for a prospective, investigator-initiated, double-blinded, randomized, placebo-controlled trial.
BACKGROUND
Chronic cluster headache (CCH) is a debilitating primary headache disorder. Occipital nerve stimulation (ONS) has shown the potential to reduce attack frequency, but the occipital paresthesia evoked by conventional (tonic) stimulation challenges a blinded comparison of active stimulation and placebo. Burst ONS offers paresthesia-free stimulation, enabling a blinded, placebo-controlled study. Identification of a feasible preoperative test would help select the best candidates for implantation. This study aims to explore ONS as a preventive treatment for CCH, comparing burst stimulation to tonic stimulation and placebo, and possibly identifying a potential preoperative predictor.
METHODS
An investigator-initiated, double-blinded, randomized, placebo-controlled trial is conducted, including 40 patients with CCH. Eligible patients complete a trial with the following elements: I) four weeks of baseline observation, II) 12 weeks of transcutaneous electrical nerve stimulation (TENS) of the occipital nerves, III) implantation of a full ONS system followed by 2 week grace period, IV) 12 weeks of blinded trial with 1:1 randomization to either placebo (deactivated ONS system) or burst (paresthesia-free) stimulation, and V) 12 weeks of tonic stimulation. The primary outcomes are the reduction in headache attack frequency with TENS and ONS and treatment safety. Secondary outcomes are treatment efficacy of burst versus tonic ONS, the feasibility of TENS as a predictor for ONS outcome, reduction in headache pain intensity (numeric rating scale), reduction in background headache, the patient's impression of change (PGIC), health-related quality of life (EuroQoL-5D), self-reported sleep quality, and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). Data on headache attack characteristics are registered weekly. Data on patient-reported outcomes are assessed after each trial phase.
DISCUSSION
The study design allows a comparison between burst ONS and placebo in refractory CCH and enables a comparison of the efficacy of burst and tonic ONS. It will provide information about the effect of burst ONS and explore whether the addition of this stimulation paradigm may improve stimulation protocols. TENS is evaluated as a feasible preoperative screening tool for ONS outcomes by comparing the effect of attack prevention of TENS and tonic ONS.
TRIAL REGISTRATION
The study is registered at Clinicaltrials.gov (trial registration number NCT05023460, registration date 07-27-2023).
Topics: Humans; Transcutaneous Electric Nerve Stimulation; Cluster Headache; Quality of Life; Prospective Studies; Headache; Treatment Outcome; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 37865755
DOI: 10.1186/s12883-023-03435-9 -
Journal of Cachexia, Sarcopenia and... Jun 2024Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary... (Review)
Review
Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.
Topics: Humans; Cachexia; Neoplasms; Body Composition; Body Weight; Clinical Trials as Topic
PubMed: 38738581
DOI: 10.1002/jcsm.13478 -
Trials Aug 2023Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed....
Effectiveness of group arts therapies (art therapy, dance movement therapy and music therapy) compared to group counselling for diagnostically heterogeneous psychiatric community patients: study protocol for a randomised controlled trial in mental health services (the ERA study).
BACKGROUND
Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed. Trials to date have been limited to one art-form or diagnosis. Patients may hold strong preferences for or against an art-form whilst group therapies rely on heterogeneity to provide a range of learning experiences. This study will test whether manualised group arts therapies (art therapy, dance movement therapy and music therapy) are effective in reducing psychological distress for diagnostically heterogeneous patients in community mental health compared to active group counselling control.
METHODS
A pragmatic multi-centre 2-arm randomised controlled superiority trial with health economic evaluation and nested process evaluation. Adults aged ≥ 18, living in the community with a primary diagnosis of psychosis, mood, or anxiety disorder will be invited to participate and provide written informed consent. Participants are eligible if they score ≥ 1.65 on the Global Severity Index of the Brief Symptom Inventory. Those eligible will view videos of arts therapies and be asked for their preference. Participants are randomised to either their preferred type of group arts therapy or counselling. Groups will run twice per week in a community venue for 20 weeks. Our primary outcome is symptom distress at the end of intervention. Secondary outcomes include observer-rated symptoms, social situation and quality of life. Data will be collected at baseline, post-intervention and 6 and 12 months post-intervention. Outcome assessors and trial statisticians will be blinded. Analysis will be intention-to-treat. Economic evaluation will assess the cost-effectiveness of group arts therapies. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of group process measures and qualitative interviews with participants and therapists.
DISCUSSION
This will be the first trial to account for patient preferences and diagnostic heterogeneity in group arts therapies. As with all group therapies, there are a number of logistical challenges to which we have had to further adapt due to the COVID-19 pandemic. Overall, the study will provide evidence as to whether there is an additive benefit or not to the use of the arts in group therapy in community mental health care.
TRIAL REGISTRATION
ISRCTN, ISRCTN88805048 . Registered on 12 September 2018.
Topics: Adult; Humans; Art Therapy; Counseling; COVID-19; Dance Therapy; Mental Health Services; Multicenter Studies as Topic; Music Therapy; Pandemics; Quality of Life; Randomized Controlled Trials as Topic; Adolescent; Pragmatic Clinical Trials as Topic; Equivalence Trials as Topic
PubMed: 37626418
DOI: 10.1186/s13063-023-07232-0