E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The principal objectives are to determine whether: 1. lower dose oral amoxicillin treatments is as effective as higher dose oral amoxicillin treatment for uncomplicated childhood pneumonia 2. shorter duration (3 days) amoxicillin treatment is as effective as longer duration (7 days) amoxicillin treatment for uncomplicated childhood pneumonia
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E.2.2 | Secondary objectives of the trial |
1. To identify the effect of amoxicillin treatment on the development of penicillin resistance. 2. To assess side effects (especially skin rashes and diarrhoea) and the severity and duration of symptoms of pneumonia. 3. To examine patient-related outcomes including days off work for carers and days away from out-of-home childcare. 4. To determine the cost implications of dose and duration of amoxicillin treatment for pneumonia as inpatients and outpatients. 5. To assess the cumulative number of additional courses of antibiotics and total number of days of re-treatment with antibiotics 6. Adherence to trial drug |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The inclusion criteria are different for the patients recruited from PED and from the WARD settings therefore these have been displayed here separately. PED Group: 1. Age from 1 to 5 years (up to their 6th birthday) 2. Clinical diagnosis of CAP as defined by all the following: Presence of cough (reported by parents/guardians in last 96 hours) AND Temperature ≥38oC measured by any method or history of fever in last 24 hours reported by parents/guardians AND Signs of laboured/difficult breathing or focal chest signs at presentation in the PED (i.e. one or more of the following): o Nasal flaring o Chest retractions o Abdominal breathing o Focal dullness to percussion o Focal reduced breath sounds o Crackles with asymmetry 3. Decision to treat with oral amoxicillin for CAP on discharge from hospital 4. Parent/guardian willing to accept all possible randomised allocations 5. Available for follow-up for the entire study period, parent/guardian willing to be contacted by telephone at day 4, weeks 1, 2 and 3, and attend a face-to-face follow up visit at 4 weeks after randomisation 6. Informed consent form for trial participation signed by parent/guardian.
WARD: 1. Age from 1 to 5 years (up to their 6th birthday) 2. Clinical diagnosis of CAP as defined by the all the following : o Presence of cough (reported by parents/guardians in last 96 hours) AND; o Temperature ≥38oC measured by any method or history of fever in last 24 hours reported by parents/guardians AND; o Signs of laboured/difficult breathing or focal chest signs (i.e. one or more of the following): Nasal flaring Chest retractions Abdominal breathing Focal dullness to percussion Focal reduced breath sounds Crackles with asymmetry 3. Admitted to a paediatric assessment unit or inpatient ward at a participating hospital 4. Treated with any oral or intravenous beta-lactam for ≤48 hours after admission 5. Decision to further treat with oral amoxicillin for CAP 6. Planned for discharge and to continue uninterrupted antibiotic treatment. 7. Available for follow-up for the entire study period, parent/guardian willing to be contacted by telephone at weeks 1, 2 and 3 and attend face-to-face follow up visit at 4 weeks after randomisation. 8. Parent/guardian willing to accept all possible randomised allocations 9. Informed consent for trial participation signed by a parent/guardian
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E.4 | Principal exclusion criteria |
The exclusion criteria are different for the patients recruited from PED and from the WARD settings therefore these have been displayed here separately. PED Group: 1. Severe underlying chronic disease including sickle cell anaemia, primary or secondary immunodeficiency, chronic lung disease and cystic fibrosis 2. Documented penicillin allergy 3. Any other known contra-indication to amoxicillin 4. On systemic antibiotic treatment at presentation 5. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology) 6. Complicated pneumonia 7. Initial decision to treat with oral antibiotic other than amoxicillin on discharge from hospital 8. Receipt of initial antibiotic treatment as inpatient in PAU or on the ward* 9. Weight >24kg 10. Parents/guardians unlikely to reliably complete the diary because of significant language barriers.
WARD: 1. Severe underlying chronic disease including sickle cell anaemia, primary or secondary immunodeficiency, chronic lung disease and cystic fibrosis 2. Documented penicillin allergy 3. Any other known contra-indication to taking amoxicillin 4. Already on systemic antibiotic treatment at presentation 5. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology) 6. Complicated pneumonia 7. Receipt of antibiotic other than a beta-lactam during admission 8. Clinically relevant positive blood culture (i.e. positive blood culture and clinical decision to prolong intravenous treatment for more than 48 hours or inappropriate to switch to amoxicillin therapy) 9. Current oxygen requirement 10. Current age-specific tachypnoea 11. Receipt of >48 hours oral or intravenous inpatient antibiotic treatment 12. Decision to treat with oral antibiotic other than amoxicillin on discharge from hospital 13. Weight >24kg 14. Parents/guardians unlikely to reliably complete the diary because of significant language barriers. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Any antibiotic treatment prescribed in addition to the allocated trial medication as an inpatient or outpatient up to and at final follow-up. This includes retreatment, extension of treatment and treatment with additional antibiotics. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 31 |