Acute episodes of Pneumonia and sepsis in older adults MedDRA version: 14.1 Level: PT Classification code 10035664 Term: Pneumonia System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Simastatin (zocor) 80mg once daily
Product Name: Simvastatin
Product Code: PL0025/0366
Pharmaceutical Form: Capsule
INN or P
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Age > 60 years 2. Patients with a diagnosis of community acquired pneumonia. We will use the British Thoracic Society definition of pneumonia; defined as “symptoms and signs consistent with an acute lower respiratory tract infection associated with new radiographic shadowing for which there is no other explanation”. We will include symptoms and signs as having 3 or more of the following: cough, sputum production, breathlessness, pleuritic chest pain, haemoptysis, fever, headache, signs consistent with pneumonia on chest auscultation. 3. Pneumonia patients will also need to meet the criteria for sepsis based on the standard definitions as published in the 2008 Surviving Sepsis Campaign Guidelines. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 46
Exclusion criteria
Exclusion criteria: Exclusion criteria • More than 48 hours from admission at time of consent. • Current or recent statin use within 1 month. • known prior myositis. • creatinine kinase >10 times upper limit normal range* • transaminases (ALT/AST) >8 times upper limit of normal range* • severe renal impairment (creatinine clearance <30ml/min) not receiving renal replacement therapy • patients currently receiving ongoing and sustained treatment with any of the following: itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, ciclosporine, amiodarone, verapamil or diltiazem. Fibric acid derivatives (except fenofibrate), danazol. • A family history of muscular disorders. • Known HIV or hepatitis B/C infection. • Contraindication to enteral drug administration (either PO or Per NG) e.g. patients with mechanical bowel obstruction. • Known participation in other investigational medicinal product (IMP_ trials within 30 days. • Consent / relative or advocate assent declined. • Treatment withdrawal imminent within 24 hours. •Immunosuppression due to corticosteroid or other immunosuppressant use • Patient declines consent • Personal Consultee, when available, does not provide assent • Porfessional Consultee, if used, does not provide assent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Pneumonia (severe lung infection) is one of the commonest causes of death and the death rate has not fallen for many years. Elderly patients are at greater risk of pneumonia and its complications such as sepsis. Usually the immune system works cooperatively to clear infection and prevent organ damage. Neutrophils are cells of the immune system that are critical in clearing bacteria. These cells are the foot soldiers of the immune system and move from the blood into infected tissues/organs to locate and kill the invading bacteria using an arsenal of toxic products. Sepsis occurs when the bodies normally helpful reaction to infection becomes harmful. As part of this process, neutrophils stop working properly, they become less able to clear bacteria and release their toxic products indiscriminately, causing organ damage. Defects in the efficiency of these cells is associated with a poor outcome from pneumonia and sepsis. We have undertaken a pilot study in patients, which;Secondary Objective: 1) safety and tolerability of drug in this patient group. 2) relationship of baseline and changes in above to clinical relevant outcomes (survival, development of organ failure, admission to ITU, SOFA score, ventilator free days. 3) do simvastatin influence neutrophil function in cells that have transmigrated across the alveolar epithelium. 4) does simvastatin modulate biomarkers of inflammation and cellular dysfunction in plasma and bronchoalveolar lavage fluid? These assessments will be made at baseline and upon day 4, 7 and convalescent samples.;Primary end point(s): The primary outcome measure is changes to key neutrophil functions in older people with pneumonia and sepsis using Simvastatin. These functions include 1. Assessment of adhesion, chemokinesis and chemotaxis by neutrophils Neutrophil adhesion and migration will be assessed in a microscopy slide based system using established methodology (35). Chemoattractants used will be those that act vi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety and tolerability of drug in this patient group. 2) Relationship of baseline and changes in above to clinical relevant outcomes (survival, development of organ failure,admission to ITU, SOFA score, ventilator free days).;Timepoint(s) of evaluation of this end point: Day 0, 4, 7 and re-cooperation sample at day 14 | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Coordinator
Queen Elizabeth Hospital Birmingham NHS Trust
Outcome results
None listed