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BackgroundMultiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. MethodsWe conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. ConclusionEarly administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. (Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca; ClinicalTrials.gov number, NCT04416399) Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed. Added value of this studyIn this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care. Implications of all the available evidenceThe STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.
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BackgroundThe COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within 24-48 hours of their test result. MethodsA multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (within 24-48 hours of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology. ResultsPrior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1,013 recruits to PRINCIPLE at the start of October 2020 to 2,802 recruits by 20th December 2020. While procedural caveats were identified by the public consultation, out of 2,639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached. ConclusionsThis paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment, and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions. Trial registrationPRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 ISRCTN registry: ISRCTN86534580 REC number: 20/SC/058 IRAS number: 281958
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BACKGROUND@#Patient reported outcome measures assess clinical progress from the patient's perspective. This study explored the relationship between shoulder outcome measures (The Disability of the Arm, Shoulder and Hand [DASH], American Shoulder and Elbow Surgeons Standard Shoulder Assessment score [ASES], and Constant score) by comparing the best possible scores obtained in an asymptomatic population compared to overall perception of health, as measured by the SF-36 outcome measure.@*METHODS@#Volunteers (age range, 20–69 years) with asymptomatic shoulders and no history of shoulder pain, injury, surgery, imaging, or pathology (bilaterally) were included. The DASH and ASES measures were completed by 111 volunteers (72 female, 39 male), of which 92 completed the Constant score (56 female, 36 male). The SF-36 was completed by all volunteers (level of evidence: IV case series).@*RESULTS@#The mean (x̄) score for ASES measure on the right shoulder was higher for the left-hand dominant side (x̄=100.00 vs. 95.02, p-value<0.001); no other significant differences. Better SF-36 scores were associated with better DASH scores. Our prediction models suggest that perception of overall health affects the DASH scores. Sex affected all three shoulder measures scores.@*CONCLUSIONS@#Comparing scores of shoulder outcome measures to the highest possible score is not the most informative way to interpret patient progress. Variables such as health status, sex, and hand dominance need to be considered. Furthermore, it is possible to use these variables to predict scores of outcome measures, which facilitates the healthcare provider to deliver individualized care to their patients.
