Additional file 1 of Sample size calculation in randomised phase II selection trials using a margin of practical equivalence

Additional file 1. Sample size calculation in randomised phase II selection trials using a margin of practical equivalence

sj-pdf-1-ctj-10.1177_17407745241240401 – Supplemental material for The 3 + 3 design in dose-finding studies with small sample sizes: Pitfalls and possible remedies

Supplemental material, sj-pdf-1-ctj-10.1177_17407745241240401 for The 3 + 3 design in dose-finding studies with small sample sizes: Pitfalls and possible remedies by Cody Chiuzan and Hakim-Moulay Dehbi in Clinical Trials</p

Data_Sheet_1_A Double-Blind Placebo-Controlled Crossover Study of the Effect of Beetroot Juice Containing Dietary Nitrate on Aortic and Brachial Blood Pressure Over 24 h.docx

Dietary inorganic nitrate in beetroot can act as a source of nitric oxide and has been reported to lower brachial blood pressure (BP). This study examined the effect of inorganic nitrate in beetroot juice on aortic (central) BP acutely and over the subsequent 24-h period. A double blind, randomized, placebo-controlled crossover trial was performed in fifteen healthy, normotensive men and women (age 22–40 years). Participants were randomized to receive beetroot juice containing nitrate (6.5–7.3 mmol) or placebo beetroot juice from which nitrate had been removed (<0.06 mmol nitrate). Effects on aortic systolic BP were measured at 30 min (primary endpoint), 60 min and over a subsequent 24 h period using an ambulatory BP monitor. Carotid-femoral pulse wave velocity (cfPWV) was also measured at 30 min. Following a washout period, the procedure was repeated within 7 days with crossover to the opposite arm of the trial. Compared with placebo, ingestion of beetroot juice containing nitrate lowered aortic systolic BP at 30 min by 5.2 (1.9–8.5) mmHg [mean (95% confidence interval); p < 0.01]. A smaller effect on aortic systolic BP was observed at 60 min. There were minimal effects on brachial BP or cfPWV. Effects on aortic systolic BP were not sustained over the subsequent 24 h and there were no effects on other hemodynamic parameters during ambulatory monitoring. A single dose of beetroot juice containing nitrate lowers aortic BP more effectively than brachial BP in the short term, but the effects are comparatively short-lived and do not persist over the course of the same day.</p

Finger-Prick Autologous Blood (FAB) Eye Drops for Dry Eye Disease: Single Masked Multi-Centre Randomised Controlled Trial

Purpose: To investigate the quantitative and qualitative efficacy of finger-prick autologous blood (FAB) eye drops versus conventional medical therapy for the treatment of severe dry eye disease (DED). Methods: Two centre, single masked, randomised controlled trial. Sixty patients in total were recruited with thirty patients (sixty eyes) treated with FAB eye drops four times per day in addition to their conventional DED treatment, and thirty patients (fifty-eight eyes) served as control subjects on conventional treatment alone. Ocular surface disease index (OSDI), Schirmer’s test, fluorescein ocular staining grade (OCSG) Oxford schema and fluorescein tear film break-up time (TBUT), were performed at baseline, at 4 and 8 weeks. Results: OSDI scores significantly decreased in the FAB arm by greater than -17.68 (-37.67 to -2.96, p=0.02) compared to the control arm. There were greater improvements in OCSG and TBUT in the FAB arm but these were non-significant (p>0.05). Conclusion: This feasibility study demonstrates adding FAB eye drops to conventional medical therapy for DED improves mean OSDI symptom score compared to conventional medical therapy alone. It may have particular use in settings where serum is unobtainable. An adequately powered and well-designed randomised trial is needed to further evaluate the long-term clinical benefit of FAB.</p

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Schedule of assessments in the STIMULATE-ICP trial.

Consent for data collection only may take place before first clinic visit and up to 10 days post clinic. Consent for drug arm must be at clinic visit (to assess eligibility based on clinic record) or in the 7 days post clinic. This is to align the administration on IMP with follow-up data collection and clinic pathway. Consent for research blood to be taken at either time point as per patient choice. **Coverscan as usual care for allocated clusters. ***: Assessment 1 is 12 weeks from baseline visit date (date of randomisation or first dose of study IMP) or consent date at baseline visit (if only consented to data collection). ****: Follow up assessment 24 weeks from baseline visit date (date of randomisation or first dose of study IMP) or consent date at baseline visit (if only consented to data collection). 1: If requested by the treating physician at Long COVID Clinics as part of their routine care. 2: Only if recruited from a site randomised to Coverscan™ cluster. 3: If randomised to receive the trial drug. 4: if the participant scores ≥3 on PDQ5 questionnaire. 5: For female participants of childbearing potential randomised to drug arm of the trial. 6: blood samples collected for functional T cell and live virus neuralisation assays from London Participants only at baseline and 12 weeks. All other participating centres will collect blood for external laboratory analysis once at baseline visit. Permission will be sort from all participants to recontact to participate in further testing due to any changes to the study on the basis of emerging evidence/results. 7. concomitant medications will be reviewed at 12 and 24 weeks visit is only for participants o the nested drug trial. b. Adverse events will be collected at the 24 week visit for participants on the nested drug trial only.</p

The STIMULATE-ICP programme showing the interconnections between the Trial and other work packages.

Abbreviations: COVID: COrona Virus Disease; FAS: Fatigue Assessment Scale; PCN: Primary Care Network; PRO: Patient-Reported Outcome; WP: Work Package.</p

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