Phase III parallel-group, randomised, double blind clinical trial, performed in 31 primary healthcare centres in Spain.
The use of narrow-spectrum antibiotics is needed because of the dearth of new antimicrobials and the link observed between the consumption of broad-spectrum antibiotics and the emergence and spread of antibacterial resistance.
Objective: The aim of the present trial was to determine whether high-dose penicillin V was as effective as high-dose amoxicillin for the treatment of uncomplicated CAP in a Mediterranean adult population.
Subjects: Patients between 18-75 years with lower respiratory tract infection and radiologically confirmed diagnosis of pneumonia.
Primary outcome: Clinical resolution at day 14
Visit Schedule: Initiation visit, day 3 phone call, day 14 presential visit, day 30 presential visit.
Quality: The study will be conducted in accordance with the principles of the Declaration of Helsinki, ICH Guidelines for GCP and in full conformity with relevant regulations. The study has been approved by the Ethical Committee of Investigation in Primary Care (Fundació d'Investigació en Atenció Primària) and by the Agencia Española del Medicamento y Productos Sanitarios. The study data was fully monitored by speciallized personnel.
Sample size: The objective of the study is to demonstrate that penicillin V is not inferior to amoxicillin. Considering a success rate of 85% for the group treated with amoxicillin \[1,2\]. A total of 105 patients will be required in each treatment group (total of 210) to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%.
Statistical analyses:The intention-to-treat (ITT) population included all randomized patients receiving at least one dose of study drug and the per-protocol (PP) population included patients who received no systemic antimicrobial agents other than the study drug for at least three days in the case of clinical failure or ≥80% of study medication in the case of cure, with adequate assessment of compliance and absence of major protocol violations.
To evaluate the comparability of the groups the two groups will be analysed with variables expressed as means and standard deviations for the case of quantitative variables and with proportions in the case of qualitative variables. The variable of the principle result, clinical cure, will be expressed as percentages and the comparison of percentages in the two treatment groups will be analysed using the Chi-square test. Logistic regression will be performed for the analysis of the predictive factors of cure or not, with calculation of the odds ratio for each of the variables analysed and multiadjustment for each of the factors of the study with confidence intervals of 95%. Variables with a p\<0.20 on bivariant analysis will be included in the analysis. A p value \< 0.05 will be considered statistically significant.
The protocol of the study has been published (3)
