P4 Peptide in Community Acquired Pneumonia

Completed

• Conditions: Pneumonia
• Interventions: Procedure: Venepuncture; Procedure: Bronchoscopy

• Registration Number: NCT03497962
• Lead Sponsor: Liverpool University Hospitals NHS Foundation Trust

Brief 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).

Detailed 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 Timeline

• Study Start: 2013-01
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Study First Submitted: 2015-05-08
• Status Verified: 2017-05
• Study First Submitted QC: 2018-04-10
• Last Update Submitted: 2018-04-10
• Study First Posted: 2018-04-13
• Last Update Posted: 2018-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ITU patients	Venepuncture	25 patients will be recruited from the Intensive Care Unit/ High dependency unit Inclusion- Adults (\>18years) with community acquired pneumonia (CAP).
ITU patients	Bronchoscopy	25 patients will be recruited from the Intensive Care Unit/ High dependency unit Inclusion- Adults (\>18years) with community acquired pneumonia (CAP).
Healthy volunteer	Bronchoscopy	24 healthy adult volunteers will be recruited to establish a comparison data set and to extend the laboratory observations to include other bacterial pathogens.
Healthy volunteer	Venepuncture	24 healthy adult volunteers will be recruited to establish a comparison data set and to extend the laboratory observations to include other bacterial pathogens.

Primary Outcome Measures

Name	Time	Method
Does P4 peptide augment phagocytic function in patients with severe community aquired pneumonia	12 hours	Opsonophagocytic killing assay performed on blood neutrophils and BAL macrophages. Neutrophils and macrophages are stimulated with P4, control is unstilumated neutrophils and macrophages. The comparison is made between the killing of pneumococcal bacteria between the stimulated and unstimulated cells.

Trial Locations

Locations (1)

Royal Liverpool University Hospital; 🇬🇧 Liverpool, Merseyside, United Kingdom