Immediate oral versus immediate topical versus delayed oral antibiotics for children with acute otitis media with discharge: the REST three-arm non-inferiority electronic platform-supported RCT

Health Technology Assessment

Jodi Taylor¹  Annie Sadoo¹  Sue Harris¹  Sian Noble¹  Kate Rowley¹  Richard Morris¹  Kathryn Curtis¹  Nicholas Turner¹  Jeremy Horwood²  Alastair D Hay²  Christie Cabral²  Andrew Lovering³  Brendan Delaney⁴  Anne Schilder⁵  Roger Damoiseaux⁶  Roderick Venekamp⁶  Paul Little⁷  Michael V Moore⁷  Scott Wilkes⁸  Jesús Domínguez⁹  Vasa Curcin⁹  Archana Tapuria⁹  Vibhore Prasad⁹ 

[1] Bristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK;Centre for Academic Primary Care, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK;Department of Medical Microbiology, North Bristol NHS Trust, Bristol, UK;Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK;Ear Institute, University College London, London, UK;Julius Center for Health Sciences and Primary Care & Department of Otorhinolaryngology, UMC Utrecht, Utrecht, the Netherlands;Primary Care and Population Sciences, University of Southampton, Southampton, UK;School of Medicine, University of Sunderland, Sunderland, UK;School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK;

关键词: acute otitis media;    primary care;    antibiotics;    paediatrics;   

DOI  :  10.3310/hta25670

来源: DOAJ

【 摘 要 】

Background: Acute otitis media is a painful infection of the middle ear that is commonly seen in children. In some children, the eardrum spontaneously bursts, discharging visible pus (otorrhoea) into the outer ear. Objective: To compare the clinical effectiveness of immediate topical antibiotics or delayed oral antibiotics with the clinical effectiveness of immediate oral antibiotics in reducing symptom duration in children presenting to primary care with acute otitis media with discharge and the economic impact of the alternative strategies. Design: This was a pragmatic, three-arm, individually randomised (stratified by age < 2 vs. ≥ 2 years), non-inferiority, open-label trial, with economic and qualitative evaluations, supported by a health-record-integrated electronic trial platform [TRANSFoRm (Translational Research and Patient Safety in Europe)] with an internal pilot. Setting: A total of 44 English general practices. Participants: Children aged ≥ 12 months and < 16 years whose parents (or carers) were seeking medical care for unilateral otorrhoea (ear discharge) following recent-onset (≤ 7 days) acute otitis media. Interventions: (1) Immediate ciprofloxacin (0.3%) solution, four drops given three times daily for 7 days, or (2) delayed ‘dose-by-age’ amoxicillin suspension given three times daily (clarithromycin twice daily if the child was penicillin allergic) for 7 days, with structured delaying advice. All parents were given standardised information regarding symptom management (paracetamol/ibuprofen/fluids) and advice to complete the course. Comparator: Immediate ‘dose-by-age’ oral amoxicillin given three times daily (or clarithromycin given twice daily) for 7 days. Parents received standardised symptom management advice along with advice to complete the course. Main outcome measure: Time from randomisation to the first day on which all symptoms (pain, fever, being unwell, sleep disturbance, otorrhoea and episodes of distress/crying) were rated ‘no’ or ‘very slight’ problem (without need for analgesia). Methods: Participants were recruited from routine primary care appointments. The planned sample size was 399 children. Follow-up used parent-completed validated symptom diaries. Results: Delays in software deployment and configuration led to small recruitment numbers and trial closure at the end of the internal pilot. Twenty-two children (median age 5 years; 62% boys) were randomised: five, seven and 10 to immediate oral, delayed oral and immediate topical antibiotics, respectively. All children received prescriptions as randomised. Seven (32%) children fully adhered to the treatment as allocated. Symptom duration data were available for 17 (77%) children. The median (interquartile range) number of days until symptom resolution in the immediate oral, delayed oral and immediate topical antibiotic arms was 6 (4–9), 4 (3–7) and 4 (3–6), respectively. Comparative analyses were not conducted because of small numbers. There were no serious adverse events and six reports of new or worsening symptoms. Qualitative clinician interviews showed that the trial question was important. When the platform functioned as intended, it was liked. However, staff reported malfunctioning software for long periods, resulting in missed recruitment opportunities. Troubleshooting the software placed significant burdens on staff. Limitations: The over-riding weakness was the failure to recruit enough children. Conclusions: We were unable to answer the main research question because of a failure to reach the required sample size. Our experience of running an electronic platform-supported trial in primary care has highlighted challenges from which we have drawn recommendations for the National Institute for Health Research (NIHR) and the research community. These should be considered before such a platform is used again. Trial registration: Current Controlled Trials ISRCTN12873692 and EudraCT 2017-003635-10. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 67. See the NIHR Journals Library website for further project information.

【 授权许可】

Unknown