Clinical Trials Logo

Clinical Trial Summary

The investigators' aim is to find out whether immune cells from patients with a severe chest infection will react ex vivo to a new immunomodulating peptide, P4 as part of augmented passive immunotherapy

The investigators know that P4 treatment can successfully improve the efficiency of specialized immune cells responsible for killing bacteria. The investigators also know that P4 treatment is effective in healthy human volunteers but wish to extend this observation to patients that have infection, as immune cells may react differently in these patients. If this study is successful, the investigators hope to be moving closer to a new treatment against severe bacterial infections.

The investigators plan to recruit patients admitted to the Intensive Care Unit (ICU) and healthy volunteers, using carefully established inclusion and exclusions criteria with severe community acquired pneumonia (CAP) and obtain both blood and (if clinically feasible), a bronchoscopy BAL sample (washing of lung tissue).


Clinical Trial Description

The investigators will examine the response to P4 peptide of alveolar macrophages from bronchoalveolar lavage (BAL) and neutrophils from peripheral blood collected from patients with severe pneumonia admitted to the ITU.

The investigators expect to show improved phagocytosis, oxidative burst, cellular activation (flow cytometry, electron microscopy, cytokine production, transcriptomics) and bacterial killing when P4 is used to stimulate immune cells and this may lead to a novel approach to the treatment of severe infections.

The investigators will also examine the effect of P4 on alveolar macrophages and neutrophils from healthy volunteers in order to ensure comparability with previously published results and extend observations using S.pneumoniae to other causes of severe pneumonia including E.coli, Salmonellae, M.tuberculosis and Pseudomonas.

Augmented passive immunotherapy (API) is a novel potential treatment strategy to combat fulminant bacterial infections. It consists of two components

1. a peptide that enhances bacterial uptake and killing by phagocytes.

2. exogenous antibody (provided with intravenous immunoglobulin, a licensed medicinal product) which optimizes the phagocytosis. Previous studies of API have included extensive murine studies of acute and chronic bacterial infection with several different organisms. P4 has also been tested in aged mice and in mucosal administration.

The investigators will recruit patients with severe community acquired pneumonia on ICU and healthy volunteers using carefully established inclusion and exclusions criteria.

This research seeks to establish proof-of-concept for augmented passive immunotherapy in patients with severe pneumonia. Patients with mild to moderate pneumonia often respond to antibiotic therapy but those with severe community-acquired pneumonia who require admission to Intensive Care have a hospital mortality of 49.4%, despite antibiotics and optimal supportive care. These patients represent 6% of all admissions to Intensive Care Units in the UK. Strategies to improve clinical outcome for this group of patients are much needed and the investigators' research cohort has been selected to represent this group. The immunological characteristics of patients with overwhelming sepsis are likely to differ from patients with milder infection. Immune cells taken from patients with milder forms of sepsis may not respond to in vitro stimulation in the same way as cells taken from severely septic patients and therefore should not be used to establish proof-of-concept for a therapy intended for critically ill patients on Intensive Care. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03497962
Study type Observational
Source Royal Liverpool and Broadgreen University Hospitals NHS Trust
Contact
Status Completed
Phase
Start date January 2013
Completion date April 2014

See also
  Status Clinical Trial Phase
Recruiting NCT02638649 - Prehospital Use of Ultrasound in Undifferentiated Shortness of Breath N/A
Active, not recruiting NCT03140163 - Screening for Pneumonia: A Comparison of Ultra Low Dose Chest CT [ULD-CT] and Conventional Chest Radiography [CXR] N/A
Completed NCT02864420 - Hospitalization at Home: The Acute Care Home Hospital Program for Adults N/A
Recruiting NCT02515565 - Physiotherapy in Patients Hospitalized Due to Pneumonia. N/A
Completed NCT02105298 - Effect of Volume and Type of Fluid on Postoperative Incidence of Respiratory Complications and Outcome (CRC-Study) N/A
Completed NCT01446926 - Study of Investigational Pneumococcal Vaccine in Healthy Adults, Toddlers and Infants Phase 1
Completed NCT01399723 - Amoxicillin Versus Benzyl Penicillin for Treatment of Children Hospitalised With Severe Pneumonia Phase 3
Completed NCT01416519 - Physiotherapy Technique Decreases Respiratory Complications After Cardiac Operation N/A
Completed NCT01416506 - Community-Acquired Pneumonia (CAP) Surveillance N/A
Completed NCT01476995 - Prognostic Indicators as Provided by the EPIC ClearView N/A
Terminated NCT02358642 - Drug to Prevent Pneumonia in the Tube Fed Phase 4
Recruiting NCT02782013 - Study of Progression of Community Acquired Pneumonia in the Hospital N/A
Completed NCT00987792 - CAPRIVI: Community Acquired Pneumonia: Treatment With Avelox® in Hospitalized Patients N/A
Terminated NCT01057758 - STATIN-VAP STATIN-VAP - STATINs and Ventilator-Associated Pneumonia Phase 3
Completed NCT00808457 - Role of Chest Ultrasound in Diagnosing and Follow-up of Pneumonia N/A
Completed NCT00369759 - An Epidemiological Study to Evaluate the RSV-Associated Lower Respiratory Track in Infections in Infants N/A
Completed NCT00372541 - Ceftriaxone Versus Chloramphenicol for Treatment of Severe Pneumonia in Children Phase 3
Terminated NCT00428051 - Colombia Epidemiologic Surveillance Study N/A
Completed NCT00373100 - The Efficacy of Zinc as Adjunct Therapy in the Treatment of Severe Pneumonia in Children Phase 3
Recruiting NCT00131196 - Functional Genomic Influences on Disease Progression and Outcome in Sepsis N/A