The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial
<strong>Introduction</strong> The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces re-consultation due to clinical deterioration in ‘at risk’ children presenting with i...
| Váldodahkkit: | , , , , , , , , , , , , , |
|---|---|
| Materiálatiipa: | Journal article |
| Giella: | English |
| Almmustuhtton: |
European Respiratory Society
2021
|
| _version_ | 1826301568758054912 |
|---|---|
| author | Wang, K Semple, MG Moore, M Tonner, S Galal, U Grabey, J Carver, T Perera, R Yu, L-M Mollison, J Farmer, A Butler, CC Harnden, A Et al. |
| author_facet | Wang, K Semple, MG Moore, M Tonner, S Galal, U Grabey, J Carver, T Perera, R Yu, L-M Mollison, J Farmer, A Butler, CC Harnden, A Et al. |
| author_sort | Wang, K |
| collection | OXFORD |
| description | <strong>Introduction</strong>
The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces re-consultation due to clinical deterioration in ‘at risk’ children presenting with influenza-like illness (ILI) in primary or ambulatory care.
<br>
<strong>Methods</strong>
‘At risk’ children aged 6 months to 12 years presenting within five days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or placebo twice daily for five days (dosing based on age +/- weight). ‘At risk’ groups included children with respiratory, cardiac, and neurological conditions. Randomisation was stratified by region and used a non-deterministic minimisation algorithm to balance age and current seasonal influenza vaccination status. Our target sample size was 650 children, which would have allowed us to detect a reduction in the proportion of children re-consulting due to clinical deterioration from 40% to 26% with 90% power and 5% two-tailed alpha error, including allowance for 25% loss to follow-up and an inflation factor of 1.041. Participants, caregivers and investigators were blinded to treatment allocation. Intention-to-treat analysis included all randomised participants with primary outcome data on re-consultation due to clinical deterioration within 28 days. Safety analysis included all randomised participants. Trial registration: ISRCTN 70714783. EudraCT 2013-002822-21.
<br>
<strong>Results</strong>
We recruited 271 children between 11 February 2015 and 20 April 2018. Primary outcome data were available for 265 children. Only 61/265 children (23.0%) re-consulted due to clinical deterioration. No evidence of a treatment effect was observed for re-consultation due to clinical deterioration (co-amoxiclav 33/133 (24.8%), placebo 28/132 (21.2%), adjusted risk ratio [RR] 1.16, 95% confidence interval [CI] 0.75 to 1.80). There was also no evidence of a difference between groups in the proportion of children for whom one or more adverse events were reported (co-amoxiclav 32/136 (23.5%), placebo 22/135 (16.3%), adjusted RR 1.45, 95% CI 0.90 to 2.34). Sixty-six adverse events were reported in total (co-amoxiclav n=37, placebo n=29). Nine serious adverse events were reported per group; none were considered related to study medication.
<br>
<strong>Conclusion</strong>
Our trial did not find evidence that treatment with co-amoxiclav reduces risk of re-consultation due to clinical deterioration in ‘at risk’ children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI. |
| first_indexed | 2024-03-07T05:34:23Z |
| format | Journal article |
| id | oxford-uuid:e3613733-ecd1-431e-b096-73e5c2446a8f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:34:23Z |
| publishDate | 2021 |
| publisher | European Respiratory Society |
| record_format | dspace |
| spelling | oxford-uuid:e3613733-ecd1-431e-b096-73e5c2446a8f2022-03-27T10:08:50ZThe early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e3613733-ecd1-431e-b096-73e5c2446a8fEnglishSymplectic ElementsEuropean Respiratory Society2021Wang, KSemple, MGMoore, MTonner, SGalal, UGrabey, JCarver, TPerera, RYu, L-MMollison, JFarmer, AButler, CCHarnden, AEt al.<strong>Introduction</strong> The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces re-consultation due to clinical deterioration in ‘at risk’ children presenting with influenza-like illness (ILI) in primary or ambulatory care. <br> <strong>Methods</strong> ‘At risk’ children aged 6 months to 12 years presenting within five days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or placebo twice daily for five days (dosing based on age +/- weight). ‘At risk’ groups included children with respiratory, cardiac, and neurological conditions. Randomisation was stratified by region and used a non-deterministic minimisation algorithm to balance age and current seasonal influenza vaccination status. Our target sample size was 650 children, which would have allowed us to detect a reduction in the proportion of children re-consulting due to clinical deterioration from 40% to 26% with 90% power and 5% two-tailed alpha error, including allowance for 25% loss to follow-up and an inflation factor of 1.041. Participants, caregivers and investigators were blinded to treatment allocation. Intention-to-treat analysis included all randomised participants with primary outcome data on re-consultation due to clinical deterioration within 28 days. Safety analysis included all randomised participants. Trial registration: ISRCTN 70714783. EudraCT 2013-002822-21. <br> <strong>Results</strong> We recruited 271 children between 11 February 2015 and 20 April 2018. Primary outcome data were available for 265 children. Only 61/265 children (23.0%) re-consulted due to clinical deterioration. No evidence of a treatment effect was observed for re-consultation due to clinical deterioration (co-amoxiclav 33/133 (24.8%), placebo 28/132 (21.2%), adjusted risk ratio [RR] 1.16, 95% confidence interval [CI] 0.75 to 1.80). There was also no evidence of a difference between groups in the proportion of children for whom one or more adverse events were reported (co-amoxiclav 32/136 (23.5%), placebo 22/135 (16.3%), adjusted RR 1.45, 95% CI 0.90 to 2.34). Sixty-six adverse events were reported in total (co-amoxiclav n=37, placebo n=29). Nine serious adverse events were reported per group; none were considered related to study medication. <br> <strong>Conclusion</strong> Our trial did not find evidence that treatment with co-amoxiclav reduces risk of re-consultation due to clinical deterioration in ‘at risk’ children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI. |
| spellingShingle | Wang, K Semple, MG Moore, M Tonner, S Galal, U Grabey, J Carver, T Perera, R Yu, L-M Mollison, J Farmer, A Butler, CC Harnden, A Et al. The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial |
| title | The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial |
| title_full | The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial |
| title_fullStr | The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial |
| title_full_unstemmed | The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial |
| title_short | The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial |
| title_sort | early use of antibiotics for at risk children with influenza like illness archie a double blind randomised placebo controlled trial |
| work_keys_str_mv | AT wangk theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT semplemg theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT moorem theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT tonners theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT galalu theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT grabeyj theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT carvert theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT pererar theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT yulm theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT mollisonj theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT farmera theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT butlercc theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT harndena theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT etal theearlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT wangk earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT semplemg earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT moorem earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT tonners earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT galalu earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT grabeyj earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT carvert earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT pererar earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT yulm earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT mollisonj earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT farmera earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT butlercc earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT harndena earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial AT etal earlyuseofantibioticsforatriskchildrenwithinfluenzalikeillnessarchieadoubleblindrandomisedplacebocontrolledtrial |