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 greater than 6 months and weighing 6 - 24kg
2. Clinical diagnosis of CAP at presentation to PED 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 likely fever in last 48 hours 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
o Lobar pneumonia on chest X-ray (if obtained)
3. Prior antibiotic treatment:
o Not on systemic antibiotic treatment at presentation OR
o Treated in the community as an outpatient with uninterrupted oral beta-lactam antibiotics for ≤ 48 hours
4. Decision to treat with oral amoxicillin for CAP on discharge from hospital
5. Parent/guardian willing to accept all possible randomised allocations
6. 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, unless discuss with MRC CTU
7. Informed consent form for trial participation signed by parent/guardian.
WARD:
1. Age greater than 6 months and weighing 6 - 24kg
2. Clinical diagnosis of CAP at presentation to hospital 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 likely fever in last 48 hours 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
o Lobar pneumonia on chest X-ray (if obtained)
3. Prior antibiotic treatment including doses administered in hospital:
- Treated in-hospital only with any oral or intravenous beta-lactam for ≤48 hours after admission
- Treated initially in the community and subsequently in hospital with any oral or intravenous beta-lactam, without interruption, for ≤48 hours in total
4. Decision to further treat with oral amoxicillin for CAP on discharge from hospital
5. Child is considered fit for discharge at time of randomisation
6. 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, unless discussed with MRC CTU
7. Parent/guardian willing to accept all possible randomised allocations
8. 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. Need for systemic treatment with an antibiotic other than amoxicillin on discharge from hospital
5. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology)
6. Complicated pneumonia
7. Receipt of initial antibiotic treatment as inpatient in PAU or on the ward
8. 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. Bilateral wheezing without focal chest signs (most likely to represent respiratory tract infection of non-bacterial aetiology)
5. Complicated pneumonia
6. Receipt of antibiotic other than a beta-lactam during admission
7. If treated in the community prior to admission, receipt of a non-beta lactam antibiotic in the community at presentation
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. Receipt of >48 hours oral or intravenous inpatient antibiotic treatment
10. Decision to treat with oral antibiotic other than amoxicillin on discharge from hospital
11. 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 clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including CAP) other than trial medication up to and at week 4 final follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint data is collected during the follow-up period from randomisation (day 0) to final visit (day 29). An Endpoint Review Committee (ERC), blinded to randomised allocations, will review all cases where the participant was prescribed non-trial systemic antibacterial treatment. The main role of the Committee is to adjudicate, based on all available data, whether the primary outcome was met. |
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E.5.2 | Secondary end point(s) |
Specified clinical adverse events (including thrush, skin rashes and diarrhoea), severity and duration of parent-reported CAP symptoms, health economics, cumulative number of additional courses of antibiotics and total number of days of re-treatment, adherence and penicillin resistance. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoint data is evaluated during the follow-up period from randomisation (day 0) to final visit (day 29) |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |