P4 Peptide in Community Acquired Pneumonia

NCT ID: NCT03497962

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 32 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2014-04-30

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.

Conditions

Pneumonia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ITU patients

25 patients will be recruited from the Intensive Care Unit/ High dependency unit Inclusion- Adults (\>18years) with community acquired pneumonia (CAP).

Venepuncture

Intervention Type: PROCEDURE

Taken from established arterial or central lines in critical care setting or by experienced clinicians if no line available and in healthy volunteers.

Bronchoscopy

Intervention Type: PROCEDURE

Broncho-alveolar lavage to obtain alveolar macrophages

Healthy volunteer

24 healthy adult volunteers will be recruited to establish a comparison data set and to extend the laboratory observations to include other bacterial pathogens.

Venepuncture

Intervention Type: PROCEDURE

Taken from established arterial or central lines in critical care setting or by experienced clinicians if no line available and in healthy volunteers.

Bronchoscopy

Intervention Type: PROCEDURE

Broncho-alveolar lavage to obtain alveolar macrophages

Interventions

Venepuncture

Taken from established arterial or central lines in critical care setting or by experienced clinicians if no line available and in healthy volunteers.

Intervention Type: PROCEDURE

Bronchoscopy

Broncho-alveolar lavage to obtain alveolar macrophages

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Adults (>18y) with community acquired pneumonia.
• Diagnosis of CAP upon hospital admission requires: Radiographic shadowing unexplained by other causes plus Symptoms/signs consistent with acute lower respiratory tract infection.

Exclusion Criteria

• Previous hospital admission within 14 days (implies hospital acquired).
• Immunocompromising comorbidity or therapy (e.g. HIV infection, chemotherapy).
• Pregnancy.
• Deemed inappropriate by responsible Intensivist. Already recruited in to an interventional study (where the study therapy may influence the results of this study).
• Failure to obtain consent.

• The patient does not require a bronchoscopy for clinical reasons
• The patient is not invasively ventilated therefore not requiring a bronchoscopy
• The patient condition deteriorates prior to bronchoscopy such that they might no longer tolerate the procedure (e.g. those progressing to require high frequency oscillation, prone-positioning, PEEP>15cmH2O or FiO2>0.8 for ventilation).
• Patient does not tolerate bronchoscopy, i.e. if there is oxygen desaturation to <90% for >60 seconds or haemodynamic disturbance during the procedure.
• The intensive care clinician responsible for the patient develops any new concerns about the safety of bronchoscopy or bronchoalveolar lavage.

• Adults (>18y).
• Able to give fully informed consent.
• Fluent English speaker.
• Non-smoking.
• Healthy adults without current illness.
• Contraindication to bronchoscopy or immunomodulatory medication.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: collaborator

Liverpool University Hospitals NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen B Gordon, Professor

Role: PRINCIPAL_INVESTIGATOR

Royal Liverpool University Hospital/ Liverpool School of Tropical Medicine

Locations

Royal Liverpool University Hospital

Liverpool, Merseyside, United Kingdom

Countries

United Kingdom

Other Identifiers

12/NW/0730

Identifier Type: -

Identifier Source: org_study_id