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
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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NIHR Journals Library
2021-11-01
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| Series: | Health Technology Assessment |
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| Online Access: | https://doi.org/10.3310/hta25670 |
| _version_ | 1818403301886001152 |
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| author | Alastair D Hay Michael V Moore Jodi Taylor Nicholas Turner Sian Noble Christie Cabral Jeremy Horwood Vibhore Prasad Kathryn Curtis Brendan Delaney Roger Damoiseaux Jesús Domínguez Archana Tapuria Sue Harris Paul Little Andrew Lovering Richard Morris Kate Rowley Annie Sadoo Anne Schilder Roderick Venekamp Scott Wilkes Vasa Curcin |
| author_facet | Alastair D Hay Michael V Moore Jodi Taylor Nicholas Turner Sian Noble Christie Cabral Jeremy Horwood Vibhore Prasad Kathryn Curtis Brendan Delaney Roger Damoiseaux Jesús Domínguez Archana Tapuria Sue Harris Paul Little Andrew Lovering Richard Morris Kate Rowley Annie Sadoo Anne Schilder Roderick Venekamp Scott Wilkes Vasa Curcin |
| author_sort | Alastair D Hay |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T08:22:05Z |
| format | Article |
| id | doaj.art-ad42f86dfc47479a80aaa18c523c7209 |
| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-12-14T08:22:05Z |
| publishDate | 2021-11-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Health Technology Assessment |
| spelling | doaj.art-ad42f86dfc47479a80aaa18c523c72092022-12-21T23:09:47ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242021-11-01256710.3310/hta2567016/85/01Immediate 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 RCTAlastair D Hay0Michael V Moore1Jodi Taylor2Nicholas Turner3Sian Noble4Christie Cabral5Jeremy Horwood6Vibhore Prasad7Kathryn Curtis8Brendan Delaney9Roger Damoiseaux10Jesús Domínguez11Archana Tapuria12Sue Harris13Paul Little14Andrew Lovering15Richard Morris16Kate Rowley17Annie Sadoo18Anne Schilder19Roderick Venekamp20Scott Wilkes21Vasa Curcin22Centre for Academic Primary Care, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKPrimary Care and Population Sciences, University of Southampton, Southampton, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKCentre for Academic Primary Care, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKCentre for Academic Primary Care, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKSchool of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UKJulius Center for Health Sciences and Primary Care & Department of Otorhinolaryngology, UMC Utrecht, Utrecht, the NetherlandsSchool of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UKSchool of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKPrimary Care and Population Sciences, University of Southampton, Southampton, UKDepartment of Medical Microbiology, North Bristol NHS Trust, Bristol, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKBristol Randomised Trials Collaboration, Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKEar Institute, University College London, London, UKJulius Center for Health Sciences and Primary Care & Department of Otorhinolaryngology, UMC Utrecht, Utrecht, the NetherlandsSchool of Medicine, University of Sunderland, Sunderland, UKSchool of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UKBackground: 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.https://doi.org/10.3310/hta25670acute otitis mediaprimary careantibioticspaediatrics |
| spellingShingle | Alastair D Hay Michael V Moore Jodi Taylor Nicholas Turner Sian Noble Christie Cabral Jeremy Horwood Vibhore Prasad Kathryn Curtis Brendan Delaney Roger Damoiseaux Jesús Domínguez Archana Tapuria Sue Harris Paul Little Andrew Lovering Richard Morris Kate Rowley Annie Sadoo Anne Schilder Roderick Venekamp Scott Wilkes Vasa Curcin 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 acute otitis media primary care antibiotics paediatrics |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | acute otitis media primary care antibiotics paediatrics |
| url | https://doi.org/10.3310/hta25670 |
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