Pilot Study of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia

Prospective, Non-controlled Pilot Study to Evaluate the Efficacy and Safety of Cefditoren Pivoxil in COVID-19 Patients With Mild to Moderate Pneumonia

The global pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, in December 2019, and has since spread worldwide. The disease is mild in 85% of cases but the remaining 15% requires hospitalization and/or intensive care.

Recent publications show that a significant number of COVID-19 patients are co-infected with one or more pathogens. Most co-infections occurred within 1-4 days of onset of COVID-19 disease and a considerable number of patients arrive to the Emergency rooms with mild-moderate respiratory symptoms compatible with pneumonia of presumed bacterial origin and not severe enough for requiring hospitalization. It therefore seems reasonable to adopt therapeutic strategies for these patients that are effective and easy to follow in the outpatient setting.

Cefditoren (CDN) is a third-generation cephalosporin for oral administration. CDN has a broad spectrum of activity and is particularly active against the bacterial pathogens involved in community respiratory tract infections. Besides that, the use of CDN has been associated with a marked decrease in circulating levels of IL-6 and other pro-inflammatory cytokines and mediators of epithelial damage. The aim of this study is to demonstrate that CDN improves clinical condition in patients with mild-moderate COVID-19 and symptoms of bacterial pneumonia.

Study Overview

• Status: Completed
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Cefditoren pivoxil 400mg

Detailed Description

The global pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, in December 2019, and has since spread worldwide. The novel coronavirus is now referred to as severe and critical acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is mild in 85% of cases but the remaining 15% requires hospitalization and/or intensive care.

Recent publications show that a variable number of COVID-19 patients are co-infected with one or more pathogens. Most co-infections occurred within 1-4 days of onset of COVID-19 disease and in a retrospective study, secondary infection was observed in 50% of non-survivor patients.

In COVID-19 patients the elevated inflammatory cytokines and other inflammatory mediators present suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of this disease. The elevated cytokine levels, specifically IL-6, may also be responsible for the lethal complications of COVID-19. Therefore, the interleukin-6 (IL-6) blockade has been proposed as one of the strategies to manage COVID-19-induced CRS.

A considerable number of COVID-19 patients arrive to the Emergency rooms with mild-moderate respiratory symptoms compatible with pneumonia of presumed bacterial origin not severe enough for requiring hospitalization. It therefore seems reasonable to adopt therapeutic strategies for these patients that are effective and easy to follow in the outpatient setting to avoid overloading the Health System.

Cefditoren (CDN) is a third-generation cephalosporin for oral administration. CDN has a broad spectrum of activity and is particularly active against the bacterial pathogens involved in community respiratory tract infections. The results of clinical trials with CDN on community-acquired pneumonia showed percentages of clinical and microbiological efficacy around 85%. On the other hand, the use of CDN has been associated with a marked decrease in circulating levels of IL-6 and other pro-inflammatory cytokines and mediators of epithelial damage such as Krebs von den Lungen-6 (KL-6).

Considering the above and the current estate of knowledge against SARS-CoV-2, we have considered of relevance to study the efficacy of CDN in a series of patients with mild-moderate COVID-19 and with symptoms compatible with pneumonia of presumed bacterial origin, seen at the Emergency room of a public hospital and followed on outpatient basis.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Coslada, Madrid, Spain, 28822
      • HU Henares

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult ≥18 years
• Positive for SARS CoV-2
• Radiological and clinical signs of mild-moderate pneumonia
• Fever ≥37.7 ºC
• Sat O2> 94% and respiratory rate <24 on admission
• Able of taking oral medication
• HIV negative
• Written and signed consent

Exclusion Criteria:

• Concomitant treatments with drugs of demonstrated or potential action against SARS CoV-2 within the previous 24 hours.
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 5 times the upper limit
• corrected QT (QTc) interval prolongation> 450 msg,
• Moderate or severe renal impairment (creatinine<50ml/min)
• Severe hepatic impairment (Child-Pugh C)
• Pregnancy or childbearing
• Allergy to penicillin or any other beta-lactam
• Primary carnitine deficiency
• Malabsorption or swallowing problems
• Inability to understand and follow study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefditoren pivoxil 400mg; Cefditoren pivoxil 400mg bid for 7 days	Drug: Cefditoren pivoxil 400mg; Cefditoren pivoxil 400mg bid for 7 days; Other Names: CDN-PI 400mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of patient status	Evolution of the status of the patient defined by the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19. This is a 0-8 score where higher scores mean a better or worse outcome.	28 days
Assessment of Clinical improvement	Evaluation of clinical condition through a Clinical Improvement questionnaire.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional visit to the Emergency room	New attendance to the hospital due to worsening	28 days
Need for hospitalization	Hospitalization due to worsening	28 days
Occurrence of adverse events	Adverse reactions	28 days

Collaborators and Investigators

• Sponsor: Meiji Pharma Spain S.A.
• Investigators: Principal Investigator: Cristóbal Rodríguez Leal, Dr, HU Henares

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): August 15, 2021
• Study Completion (Actual): August 15, 2021

Study Registration Dates

• First Submitted: January 12, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; pneumonia; outpatient; cefditoren
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents; Cefditoren pivoxil; Cefditoren
• Other Study ID Numbers: MPS-ME1207/401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No