Efficacy of i-PRF in regenerative endodontics therapy for mature permanent teeth with pulp necrosis: study protocol for a multicentre randomised controlled trial

Abstract Background Dental pulp necrosis, a common health problem, is traditionally treated with root canal therapy; however, it fails in restoring the vitality of damaged pulp. Most studies regarding regenerative endodontic therapy (RET) are limited to the treatment of immature necrotic teeth. Given that injectable platelet-rich fibrin (i-PRF) has shown great potential in regenerative medicine as a novel platelet concentration, this study is designed to explore whether i-PRF can serve as a biological scaffold, extending the indications for RET and improving the clinical feasibility of RET in mature permanent teeth with pulp necrosis. Methods This is a randomised, double-blind, controlled, multicentre clinical trial designed to evaluate the clinical feasibility of RET for mature permanent teeth with pulp necrosis and to compare the efficacy of i-PRF and blood clots as scaffolds in RET. A total of 346 patients will be recruited from three centres and randomised at an allocation ratio of 1:1 to receive RET with either a blood clot or i-PRF. The changes in subjective symptoms, clinical examinations, and imaging examinations will be tracked longitudinally for a period of 24 months. The primary outcome is the success rate of RET after 24 months. The secondary outcome is the change in pulp vitality measured via thermal and electric pulp tests. In addition, the incidence of adverse events such as discolouration, reinfection, and root resorption will be recorded for a safety evaluation. Discussion This study will evaluate the clinical feasibility of RET in mature permanent teeth with pulp necrosis, providing information regarding the efficacy, benefits, and safety of RET with i-PRF. These results may contribute to changes in the treatment of pulp necrosis in mature permanent teeth and reveal the potential of i-PRF as a novel biological scaffold for RET. Trial registration ClinicalTrials.govNCT04313010. Registered on 19 March 2020

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PEP-CoV protocol: a PEP flute-self-care randomised controlled trial to prevent respiratory deterioration and hospitalisation in early COVID-19

BMJ Open ◽

10.1136/bmjopen-2021-050582 ◽

2021 ◽

Vol 11 (6) ◽

pp. e050582

Author(s):

Annette Mollerup ◽

Sofus Christian Larsen ◽

Anita Selmer Bennetzen ◽

Marius Henriksen ◽

Mette Kildevaeld Simonsen ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Hospital Admission ◽

Usual Care ◽

Pulmonary Disease ◽

Controlled Trial ◽

Self Care ◽

Secondary Outcome ◽

Link Type ◽

Randomised Controlled ◽

At Home

IntroductionInfection with SARS-CoV-2 may progress to severe pulmonary disease, COVID-19. Currently, patients admitted to hospital because of COVID-19 have better prognosis than during the first period of the pandemic due to improved treatment. However, the overall societal susceptibility of being infected makes it pivotal to prevent severe courses of disease to avoid high mortality rates and collapse of the healthcare systems. Positive expiratory pressure (PEP) self-care is used in chronic pulmonary disease and has been shown to prevent pneumonia in a high-risk cohort of patients with leukaemia. PEP flute self-care to prevent respiratory deterioration and hospitalisation in early COVID-19: a randomised trial (The PEP-CoV trial) examines the effectiveness on respiratory symptoms and need of hospital admission by regular PEP flute use among non-hospitalised individuals with confirmed SARS-CoV-2 infection and COVID-19 symptoms.Methods and analysisIn this randomised controlled trial, we hypothesise that daily PEP flute usage as add-on to usual care is superior to usual care as regards symptom severity measured by the COPD Assessment Test (CAT) at 30-day follow-up (primary outcome) and hospital admission through register data (secondary outcome). We expect to recruit 400 individuals for the trial. Participants in the intervention group receive a kit of 2 PEP flutes and adequate resistances and access to instruction videos. A telephone hotline offers possible contact to a nurse. The eight-item CAT score measures cough, phlegm, chest tightness, dyspnoea, activities of daily living at home, feeling safe at home despite symptoms, sleep quality and vigour. The CAT score is measured daily in both intervention and control arms by surveys prompted through text messages.Ethics and disseminationThe study was registered prospectively at www.clinicaltrials.gov on 27 August 2020 (NCT04530435). Ethical approval was granted by the local health research ethics committee (Journal number: H-20035929) on 23 July 2020. Enrolment of participants began on 6 October 2020. Results will be published in scientific journals.Trial registration numberNCT04530435; Pre-results.

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Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a community-based individually randomised controlled trial in Kasaï, Democratic Republic of Congo

BMJ Open ◽

10.1136/bmjopen-2020-041213 ◽

2020 ◽

Vol 10 (12) ◽

pp. e041213

Author(s):

Cécile Cazes ◽

Kevin Phelan ◽

Victoire Hubert ◽

Rodrigue Alitanou ◽

Harouna Boubacar ◽

...

Keyword(s):

Democratic Republic ◽

Democratic Republic Of Congo ◽

Controlled Trial ◽

Acute Malnutrition ◽

Secondary Outcome ◽

Controlled Clinical Trial ◽

Medical Complication ◽

Republic Of Congo ◽

Link Type ◽

Randomised Controlled

IntroductionAcute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product—ready-to-use therapeutic food—at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6–59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <−3 or with oedema).Methods and analysisThis study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6–59 months presenting with MUAC <125 mm or WHZ <−3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes.Ethics and disseminationEthics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results for publication to a peer-reviewed journal and disseminate findings in international and national conferences and meetings.Trial registration numberNCT03751475. Registered 19 September 2018, https://clinicaltrials.gov/ct2/show/NCT03751475.

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Educational films for improving screening and self-management of gestational diabetes in India and Uganda (GUIDES): study protocol for a cluster-randomised controlled trial

Trials ◽

10.1186/s13063-021-05435-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Laura L. Oakley ◽

Deepa R ◽

Arthur Namara ◽

Biswamitra Sahu ◽

Iliatha Papachristou Nadal ◽

...

Keyword(s):

Gestational Diabetes ◽

Pregnant Women ◽

Controlled Trial ◽

Self Report ◽

Self Management ◽

Secondary Outcome ◽

Behavioural Intervention ◽

Link Type ◽

Cluster Randomised ◽

Randomised Controlled

Abstract Background The prevalence of gestational diabetes mellitus (GDM) is rising rapidly in many low- and middle-income countries (LMICs). Most women with GDM in LMICs are undiagnosed and/or inadequately managed due to a lack of knowledge and skills about GDM on the part of both providers and patients. Following contextual analysis, we developed an educational/behavioural intervention for GDM delivered through a package of culturally tailored films. This trial aims to evaluate whether the intervention can improve the timely detection and management of GDM in two LMIC settings. Methods Two independent cluster randomised controlled trials, one each to be conducted in Uganda and India. Thirty maternity facilities in each country have been recruited to the study and randomised in a 1:1 ratio to the intervention and control arms. The intervention comprises of three interconnected sets of films with the following aims: to improve knowledge of GDM guidelines and skills of health providers, to raise awareness of GDM screening among pregnant women and their families, and to improve confidence and skills in self-management among those diagnosed with GDM. In facilities randomised to the intervention arm, a GDM awareness-raising film will be shown in antenatal care waiting rooms, and four films for pregnant women with GDM will be shown in group settings and made available for viewing on mobile devices. Short films for doctors and nurses will be presented at professional development meetings. Data will be collected on approximately 10,000 pregnant women receiving care at participating facilities, with follow-up at 32 weeks gestational age and 6 weeks postnatally. Women who self-report a GDM diagnosis will be invited for a clinic visit at 34 weeks. Primary outcomes are (a) the proportion of women who report a GDM diagnosis by 32 weeks of pregnancy and (b) glycaemic control (fasting glucose and HbA1C) in women with GDM at ~34 weeks of pregnancy. The secondary outcome is a composite measure of GDM-related adverse perinatal-neonatal outcome. Discussion Screening and management of GDM are suboptimal in most LMICs. We hypothesise that a scalable film-based intervention has the potential to improve the timely detection and management of GDM in varied LMIC settings. Trial registration ClinicalTrials.gov NCT03937050, registered on 3 May 2019. Clinical Trials Registry India CTRI/2020/02/023605, registered on 26 February 2020.

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Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-021-05213-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jesus Montero-Marin ◽

◽

Elizabeth Nuthall ◽

Sarah Byford ◽

Catherine Crane ◽

...

Keyword(s):

Cost Effectiveness ◽

Randomised Controlled Trial ◽

Study Protocol ◽

Primary Endpoint ◽

Controlled Trial ◽

Mindfulness Training ◽

Secondary Outcome ◽

Link Type ◽

Randomised Controlled

Abstract Background MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at 10.1186/s13063-017-1917-4). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. Methods Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. Discussion These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design. Trial registration International Standard Randomised Controlled Trials ISRCTN86619085. Registered on 3 June 2016.

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Cholinesterase inhibitor to prevent falls in Parkinson’s disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson’s disease

BMC Neurology ◽

10.1186/s12883-021-02430-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

S. Neumann ◽

J. Taylor ◽

A. Bamford ◽

C. Metcalfe ◽

D. M. Gaunt ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cholinesterase Inhibitor ◽

Controlled Trial ◽

Secondary Outcome ◽

Fall Rate ◽

Idiopathic Parkinson’S Disease ◽

Double Blind ◽

Link Type ◽

Idiopathic Parkinson's Disease

Abstract Background Falls are a common complication of Parkinson’s disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson’s disease. Methods This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson’s disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson’s motor and non-motor symptoms, quality of life and cost-effectiveness. Discussion This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson’s disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. Trial registration REC reference: 19/SW/0043. EudraCT: 2018–003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 Protocol at time of publication Version 7.0, 20th January 2021.

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Jiao-tai-wan for insomnia symptoms caused by the disharmony of the heart and kidney: a study protocol for a randomized, double-blind, placebo-controlled trial

Trials ◽

10.1186/s13063-020-04299-x ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Congcong Zeng ◽

Xi Liu ◽

Lufeng Hu ◽

Yuan Feng ◽

Nengzhi Xia ◽

...

Keyword(s):

Clinical Trial ◽

Outcome Measures ◽

Controlled Trial ◽

Secondary Outcome ◽

Resonance Spectroscopy ◽

Double Blind ◽

Drug Intervention ◽

Double Blind Placebo ◽

Link Type ◽

Insomnia Symptoms

Abstract Background Insomnia seriously affects people’s normal lives and work. However, effective treatment strategies are scarce. The purpose of this study is to explore the efficacy and safety of Jiao-tai-wan (JTW) for ameliorating insomnia symptoms caused by disharmony of the heart and kidney. Design This is a randomized, double-blind, placebo-controlled pilot clinical trial. A total of 124 participants suffering from insomnia symptoms will be randomly assigned to the JTW or placebo group in an equal ratio. The participants will be asked to take JTW or placebo granules twice a day for 1 week. All data will be gathered at baseline and at the end of the drug intervention. The primary outcome measures will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) from baseline to the end of the drug intervention. Secondary outcome measures will include the altered sleep parameters in polysomnography, 1H-magnetic resonance spectroscopy (1H-MRS) evaluation, the Disharmony of Heart and Kidney Scoring System score, and blood tests, including the levels of serum adenosine and melatonin. A laboratory test will be taken before and after treatment to assess the safety of JTW. Discussion The outcomes of this study will confirm the efficacy of JTW for the treatment of insomnia symptoms and will also be used to monitor the safety of JTW. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019239. Registered on 1st November 2018.

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Selective versus stepwise removal of deep carious lesions in permanent teeth: a randomised controlled trial from Egypt—an interim analysis

BMJ Open ◽

10.1136/bmjopen-2019-030957 ◽

2019 ◽

Vol 9 (9) ◽

pp. e030957 ◽

Cited By ~ 2

Author(s):

Mohamed E Labib ◽

Olfat E Hassanein ◽

Makeen Moussa ◽

Asmaa Yassen ◽

Falk Schwendicke

Keyword(s):

Interim Analysis ◽

Controlled Trial ◽

Treatment Costs ◽

Permanent Teeth ◽

Secondary Outcome ◽

Spontaneous Pain ◽

Carious Lesions ◽

Tissue Removal ◽

Significant Difference ◽

Randomised Controlled

ObjectivesTo compare the success, survival and costs of selective versus stepwise carious tissue removal (SE/SW) in permanent teeth with deep (>2/3 dentine depth) carious lesions.DesignRandomised controlled, unicentre, clustered two-arm superiority trial.SettingOutpatient clinic of a private university in Cairo, Egypt.ParticipantsOne hundred and fifteen participants (n=132 teeth), aged 18–47 years, from Cairo, Egypt, were enrolled. Premolars/molars with occlusal/occlusal-proximal deep lesions (radiographically >2/3 dentine), sensible pulps, without spontaneous pain, were included.InterventionsPeripheral carious tissue removal to hard dentine was performed. Pulpo-proximally, soft dentine was left. A glass ionomer (GI) restoration was placed. After 3–4 months, teeth were randomly allocated to SE (n=66), with reduction of the GI into a base and no further tissue removal, followed by a composite resin restoration, or SW (n=66), with full removal of the GI, additional excavation until firm dentine pulpo-proximally, followed by a GI-based composite restoration. Mean follow-up was 1 year.Primary and secondary outcome measuresPrimary outcome was success (absence of endodontic/restorative complications). Secondary outcomes were tooth survival and initial and total treatment costs.ResultsZero/five pulp exposures occurred during SE/SW, and seven/five SE/SW teeth required endodontic therapy. Success after 12 months was 89.4% for SE and 84.9% for SW. The estimated mean time free of complications was 23 and 18 months for SE and SW, respectively, without significant differences between SE and SW (p>0.05/Cox). Initial treatment costs were significantly higher for SW (mean (SD): 507.5 (123.4) Egyptian pounds (EGP)) than SE (mean (SD): 456.6 (98.3) EGP), while total costs showed no significant difference (p>0.05).ConclusionWithin the limitations of this interim analysis, and considering the depth of these lesions (>2/3 dentine), SE and SW showed similar risk of failure and overall costs after 1 year.Trial registration numberPACTR201603001396248.

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Exercise for people living with frailty and receiving haemodialysis: a mixed-methods randomised controlled feasibility study

BMJ Open ◽

10.1136/bmjopen-2020-041227 ◽

2020 ◽

Vol 10 (11) ◽

pp. e041227

Author(s):

Hannah M L Young ◽

Daniel S March ◽

Patrick J Highton ◽

Matthew P M Graham-Brown ◽

Darren C Churchward ◽

...

Keyword(s):

Mixed Methods ◽

Feasibility Study ◽

Controlled Trial ◽

Exercise Programme ◽

Exercise Group ◽

Moderate Intensity ◽

Secondary Outcome ◽

Link Type ◽

Patient Reported ◽

Randomised Controlled

ObjectivesFrailty is highly prevalent in haemodialysis (HD) patients, leading to poor outcomes. This study aimed to determine whether a randomised controlled trial (RCT) of intradialytic exercise is feasible for frail HD patients, and explore how the intervention may be tailored to their needs.DesignMixed-methods feasibility.Setting and participantsPrevalent adult HD patients of the CYCLE-HD trial with a Clinical Frailty Scale Score of 4–7 (vulnerable to severely frail) were eligible for the feasibility study.InterventionsParticipants in the exercise group undertook 6 months of three times per week, progressive, moderate intensity intradialytic cycling (IDC).OutcomesPrimary outcomes were related to feasibility. Secondary outcomes were falls incidence measured from baseline to 1 year following intervention completion, and exercise capacity, physical function, physical activity and patient-reported outcomes measured at baseline and 6 months. Acceptability of trial procedures and the intervention were explored via diaries and interviews with n=25 frail HD patients who both participated in (n=13, 52%), and declined (n=12, 48%), the trial.Results124 (30%) patients were eligible, and of these 64 (52%) consented with 51 (80%) subsequently completing a baseline assessment. n=24 (71% male; 59±13 years) dialysed during shifts randomly assigned to exercise and n=27 (81% male; 65±11 years) shifts assigned to usual care. n=6 (12%) were lost to follow-up. The exercise group completed 74% of sessions. 27%–89% of secondary outcome data were missing. Frail HD patients outlined several ways to enhance trial procedures. Maintaining ability to undertake activities of daily living and social participation were outcomes of primary importance. Participants desired a varied exercise programme.ConclusionsA definitive RCT is feasible, however a comprehensive exercise programme may be more efficacious than IDC in this population.Trial registration numbersISRCTN11299707; ISRCTN12840463.

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