Clinical trial NCT03208361: Efficacy of High Doses Penicillin V Versus High Doses Amoxicillin in the Treatment of Non-severe Pneumonia.
Official title: Efficacy of High Doses of Oral Penicillin V Versus High Doses of Oral Amoxicillin in the Treatment of Non-severe Community-acquired Pneumonia in Adults
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Community-acquired Pneumonia (CAP)
Lead sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
Sponsor class: OTHER
First posted: 2017-07-05
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: Penicillin V (phenoxymethylpenicillin) Arm 2: Amoxicillin (control)
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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)

Eligibility criteria: 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

Primary outcomes:
measure: Disappearance of fever
timeFrame: 14 days after inclusion
measure: Disappearance or improvement of cough
timeFrame: 14 days after inclusion
measure: Improvement of general condition
timeFrame: 14 days after inclusion
measure: Disappearance or reduction of auscultation of crackles
timeFrame: 14 days after inclusion
measure: No other antimicrobial treatment necessary
timeFrame: 14 days after inclusion
Secondary outcomes:
measure: Disappearance of fever
timeFrame: 30 days after inclusion
measure: disappearance or improvement of cough
timeFrame: 30 days after inclusion
measure: improvement of general condition
timeFrame: 30 days after inclusion
measure: disappearance or reduction of auscultation of crackles
timeFrame: 30 days after inclusion
measure: No other antimicrobial treatment necessary
timeFrame: 30 days after inclusion
measure: Total Clinical Resolution
timeFrame: 14 days after inclusion
measure: Total Clinical Resolution
timeFrame: 30 days after inclusion
measure: Radiological resolution
timeFrame: 30 days after inclusion
measure: Adverse Events
timeFrame: 1-30 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IDIAP Jordi Gol
Study officials:
affiliation: IDIAP JORDI GOL
name: Car Llor Vilà, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aubier M, Verster R, Regamey C, Geslin P, Vercken JB. Once-daily sparfloxacin versus high-dosage amoxicillin in the treatment of community-acquired, suspected pneumococcal pneumonia in adults. Sparfloxacin European Study Group. Clin Infect Dis. 1998 Jun;26(6):1312-20. doi: 10.1086/516366.
citation: Petitpretz P, Arvis P, Marel M, Moita J, Urueta J; CAP5 Moxifloxacin Study Group. Oral moxifloxacin vs high-dosage amoxicillin in the treatment of mild-to-moderate, community-acquired, suspected pneumococcal pneumonia in adults. Chest. 2001 Jan;119(1):185-95. doi: 10.1378/chest.119.1.185.
citation: Llor C, Arranz J, Morros R, Garcia-Sangenis A, Pera H, Llobera J, Guillen-Sola M, Carandell E, Ortega J, Hernandez S, Miravitlles M. Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non-severe pneumonia attended in the community: study protocol for a randomised controlled trial. BMC Fam Pract. 2013 Apr 17;14:50. doi: 10.1186/1471-2296-14-50.