Efficacy of High Doses Penicillin V Versus High Doses Amoxicillin in the Treatment of Non-severe Pneumonia. (PENIPNEUMO)

Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina

Status and phase

Terminated

Phase 3

Conditions

Community-acquired Pneumonia (CAP)

Treatments

Drug: Penicillin V

Drug: Amoxicillin

Study type

Interventional

Funder types

Other

Identifiers

NCT03208361

2012-003511-63 (EudraCT Number)

IJG-PEN-2012

Details and patient eligibility

About

This study aims to evaluate wether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-sever community-acquired pneumonia (CAP).

Full description

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)

Enrollment

43 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients 18 years to 75 years (inclusive).
Signs and symptoms of lower respiratory tract infection.
Radiological confirmation of the diagnosis of pneumonia or not radiological confirmation but the patient has the following symptoms: high fever (> 38.5 ° C), cough and purulent sputum and auscultation of crackles in a pulmonary focus, the researcher undertakes to confirm after inclusion pneumonia with mandatory radiological study.
Signature of informed consent.

Exclusion criteria

Impaired consciousness: confused state, delirium, drowsiness, stupor or coma, at the discretion of the investigator
Respiratory rate> 30 breaths / minute
Heart rate> 125 beats / minute
Systolic blood pressure <90 mm ??Hg or diastolic BP <60 mm Hg
Hypersensitivity to beta-Lactamics
O2 saturation <92%
Axillary temperature> 40 ° C
bronchial Asthma
Pregnancy or lactation
Significant comorbidities: renal failure, liver cirrhosis, heart failure, chronic obstructive pulmonary disease, ischemic heart disease diagnosed less than 6 months, stroke diagnosed less than 6 months ago and / or type 1 diabetes mellitus
Significant alteration in chest radiography: alveolar infiltrates in more than one lobe or bilateral pleural effusion or pulmonary cavitation
Problems to meet the treatment at home: sociopathy or psychiatric problems, drug and alcohol addiction, or, an unsuitable family environment
Lack of tolerance to oral therapy: presence of nausea and vomiting, gastrectomy, post-surgery or frank diarrhea
Immunosuppression: chronic HIV infection, transplant, neutropenic, or, patients receiving immunosuppressive therapy
active malignancy
terminal disease
Hospitalization in the last month
Taking any systemic antibiotic in the previous three days or a full use of oral antibiotics prior to inclusion in the previous two weeks (use of urinary antiseptics is not a reason for exclusion).
Difficulty to attend follow-up visits
Refusal to participate in the study