START CARE: a protocol for a randomised controlled trial of step-wise budesonide-formoterol reliever-based treatment in children.

Background: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting ß2-agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed. Objective: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma. Methods: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned. Conclusion: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting ß-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.

Adverse event reporting and trial registration in venous leg ulcer trials published since the 2001 CONSORT statement revision: A systematic review.

AIM: To be in accord with the Consolidated Standards of Reporting Trials (CONSORT) Statement, all important adverse events in randomised controlled trials (RCTs) should be reported, as well as trial registration. Neither concern has been investigated in venous leg ulcer trials. We therefore aimed to quantify and explore compliance with adverse event reporting and trials registration in RCTs that reported interventions for treating venous leg ulceration. MATERIALS AND METHODS: We searched the Cochrane Controlled Trials Register, Medline, Embase, and CINAHL for studies reported between 2001 and 2017. Included studies must have been described as randomised controlled trials evaluating any intervention in a VLU population. Data was then extracted by one author into a standard form and checked by a second author. RESULTS: We screened 3100 titles and identified 204 trials involving pharmaceuticals (82), medicated and non-medicated devices (102), organisational (5) or other interventions (15) published in 76 journals. Eighty-four trials reported adverse events (41.2%), while 18 reported no events occurred (8.8%) and 78 did not report adverse events (38.2%). Types of adverse events reported included all-cause (20.1%), ulcer-related only (38.2%), treatment-related only (11.3%) and serious adverse events only (1.0%). Only 38 trials were registered (18.6%). Trial registration was associated with reporting of any adverse events (Odds Ratio 3.0, 95%CI 1.1-7.9), as was the trial being a pharmaceutical trial (Odds Ratio 2.9, 95%CI 1.5-5.7) or a multicentre trial (Odds Ratio 4.2, 95%CI 2.2-8.1). CONCLUSION: Adverse event reporting in VLU trials is variable with about one third of trials not reporting on adverse events at all. Trials registration is a the modifiable factor associated with better reporting of adverse events. Journal editors could explore how they can promote trials registration to enhance better reporting of harms in VLU trials.