STABLE trial of spectacle provision and driving safety among myopic motorcycle users in Vietnam: study protocol for a stepped-wedge, cluster randomised trial.

Background: Traffic crashes are the leading cause of death globally for people aged 5-29 years, with 90% of mortality occurring in low- and middle-income countries (LMICs). The STABLE (Slashing Two-wheeled Accidents by Leveraging Eyecare) trial was designed to determine whether providing spectacles could reduce risk among young myopic motorcycle users in Vietnam.

Methods: This investigator-masked, stepped-wedge, cluster randomised naturalistic driving trial will recruit 625 students aged 18-23 years, driving ≥ 50 km/week, with ≥ 1-year driving experience and using motorcycles as their primary means of transport, in 25 clusters of 25 students in Ho Chi Minh City, Vietnam.

Effectiveness and cost-effectiveness of a 12-month automated text message intervention for weight management in postpartum women with overweight or obesity: protocol for the Supporting MumS (SMS) multisite, parallel-group, randomised controlled trial.

Introduction: The reproductive years can increase women's weight-related risk. Evidence for effective postpartum weight management interventions is lacking and engaging women during this life stage is challenging. Following a promising pilot evaluation of the Supporting MumS intervention, we assess if theory-based and bidirectional text messages to support diet and physical activity behaviour change for weight loss and weight loss maintenance, are effective and cost-effective for weight change in postpartum women with overweight or obesity, compared with an active control arm receiving text messages on child health and development.

The Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal Compared With Conventional Lung Protective Ventilation on Cardiac Function.

Objectives: Lower tidal volume ventilation (targeting 3 mL/kg predicted body weight, PBW) facilitated by extracorporeal carbon dioxide removal (ECCOR) has been investigated as a potential therapy for acute hypoxemic respiratory failure (AHRF) in the pRotective vEntilation with veno-venouS lung assisT in respiratory failure (REST) trial. We investigated the effect of this strategy on cardiac function, and in particular the right ventricle.

Design: Substudy of the REST trial.

The relationship between plasma cystatin C, mortality and acute respiratory distress syndrome subphenotype in the HARP-2 trial.

To evaluate the performance of cystatin C as a prognostic and predictive marker in a trial of patients with acute respiratory distress syndrome (ARDS). A retrospective analysis was performed on plasma samples from patients included in the HARP-2 (hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction) trial - a multicentre, phase 2b trial carried out in general intensive care units across 40 hospitals in the United Kingdom and Ireland. Cystatin C concentrations in plasma obtained from 466 patients with ARDS (before they were randomly assigned in the trial) were quantified by ELISA (enzyme-linked immunosorbent assay).

Delivery of a novel intervention to facilitate liberation from mechanical ventilation in paediatric intensive care: A process evaluation.

Background: Prolonged mechanical ventilation increases the risk of mortality and morbidity. Optimising sedation and early testing for possible liberation from invasive mechanical ventilation (IMV) has been shown to reduce time on the ventilator. Alongside a multicentre trial of sedation and ventilation weaning, we conducted a mixed method process evaluation to understand how the intervention content and delivery was linked to trial outcomes.

School-based relationship and sexuality education intervention engaging adolescent boys for the reductions of teenage pregnancy: the JACK cluster RCT.

Background: The need to engage boys in gender-transformative relationships and sexuality education (RSE) to reduce adolescent pregnancy is endorsed by the World Health Organization and the United Nations Educational, Scientific and Cultural Organization.

Objectives: To evaluate the effects of on the avoidance of unprotected sex and other sexual health outcomes.

Design: A cluster randomised trial, incorporating health economics and process evaluations.

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.

Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148).

Heterogeneity of surrogate outcome measures used in critical care studies: A systematic review.

Background: The choice of outcome measure is a critical decision in the design of any clinical trial, but many Phase III clinical trials in critical care fail to detect a difference between the interventions being compared. This may be because the surrogate outcomes used to show beneficial effects in early phase trials (which informed the design of the subsequent Phase III trials) are not valid guides to the differences between the interventions for the main outcomes of the Phase III trials. We undertook a systematic review (1) to generate a list of outcome measures used in critical care trials, (2) to determine the variability in the outcome reporting in the respiratory subgroup and (3) to create a smaller list of potential early phase endpoints in the respiratory subgroup.

Re-analysis of ventilator-free days (VFD) in acute respiratory distress syndrome (ARDS) studies.

Background: Over recent decades, improvements in healthcare have reduced mortality and morbidity rates in many conditions. This has resulted, in part, from the identification of effective interventions in randomised trials, and in conducting such trials, a composite outcome measure (COM) with multiple components will increase event rates, which allows study completion with a smaller sample size. In critical care research, the COM "ventilator-free days" (VFD) combines mortality and duration of mechanical ventilation (MV) into a single continuous measure, which can be analysed in a variety of ways.

Standard threshold laser versus subthreshold micropulse laser for adults with diabetic macular oedema: the DIAMONDS non-inferiority RCT.

Background: The National Institute for Health and Care Excellence recommends macular laser to treat diabetic macular oedema with a central retinal subfield thickness of < 400 µm on optical coherence tomography. The DIAMONDS (DIAbetic Macular Oedema aNd Diode Subthreshold micropulse laser) trial compared standard threshold macular laser with subthreshold micropulse laser to treat diabetic macular oedema suitable for macular laser.

Objectives: Determining the clinical effectiveness, safety and cost-effectiveness of subthreshold micropulse laser compared with standard threshold macular laser to treat diabetic macular oedema with a central retinal subfield thickness of < 400 µm.

Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial.

Introduction: Lower tidal volume ventilation, facilitated by veno-venous extracorporeal carbon dioxide removal (vv-ECCOR), does not improve 90-day mortality in patients with acute hypoxaemic respiratory failure (AHRF). The aim of this analysis was to evaluate the effect of this therapeutic strategy on long-term outcomes.

Methods: This was a prespecified analysis of the REST trial, a UK-wide multicentre randomised clinical trial that compared lower tidal volume ventilation, facilitated by vv-ECCOR (intervention), with standard care in the treatment of patients with moderate-to-severe AHRF.

An external pilot cluster randomised controlled trial of a theory-based intervention to improve appropriate polypharmacy in older people in primary care (PolyPrime).

Background: For older populations with multimorbidity, polypharmacy (use of multiple medications) is a standard practice. PolyPrime is a theory-based intervention developed to improve appropriate polypharmacy in older people in primary care. This pilot study aims to assess the feasibility of the PolyPrime intervention in primary care in Northern Ireland (NI) and the Republic of Ireland (ROI).

Diabetic Macular Edema and Diode Subthreshold Micropulse Laser: A Randomized Double-Masked Noninferiority Clinical Trial.

Purpose: To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm.

Design: Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial.

Participants: Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes.

Effects of gender-transformative relationships and sexuality education to reduce adolescent pregnancy (the JACK trial): a cluster-randomised trial.

Background: The need to engage boys in gender-transformative relationships and sexuality education (RSE) to reduce adolescent pregnancy is endorsed by WHO. We aimed to test an intervention which used a gender-transformative approach to engage adolescents in RSE to prevent unprotected sex.

Methods: This cluster-randomised trial with process and economic evaluations tested a school-based intervention entitled If I Were Jack versus standard RSE (control) for students (aged 14-15 years) in UK schools.

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial.

Background: Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes.

Methods: Phase 1 is a multicentre open-label dose-escalation pilot trial.

Co-ordinated multidisciplinary intervention to reduce time to successful extubation for children on mechanical ventilation: the SANDWICH cluster stepped-wedge RCT.

Background: Daily assessment of patient readiness for liberation from invasive mechanical ventilation can reduce the duration of ventilation. However, there is uncertainty about the effectiveness of this in a paediatric population.

Objectives: To determine the effect of a ventilation liberation intervention in critically ill children who are anticipated to have a prolonged duration of mechanical ventilation (primary objective) and in all children (secondary objective).

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial.

Background: Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes.

Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure.

Design, Setting, And Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK.

Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units: A Randomized Clinical Trial.

Importance: There is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit.

Objective: To determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation.

Design, Setting, And Participants: A pragmatic multicenter, stepped-wedge, cluster randomized clinical trial was conducted that included 17 hospital sites (18 pediatric intensive care units) in the UK sequentially randomized from usual care to the protocol intervention.

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial.

Objectives: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below.

Trial Design: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis (the EASI-SWITCH trial): study protocol for a randomised controlled trial.

Background: Neutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty.