PneumoniaP4NCT03497962
P4 Peptide in Community Acquired Pneumonia
An observational study of Pneumonia, run by Liverpool University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pneumonia
- What is being tested?
- Venepuncture and Bronchoscopy
- Type of treatment
- Surgery or procedure
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2013to Apr 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients admitted into the intensive care unit with community aquired pneumonia (CAP) Healthy volunteer
Who may be able to join
- 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.
- Adults (>18y).
- Able to give fully informed consent.
- Fluent English speaker.
- Non-smoking.
- Healthy adults without current illness.
- Contraindication to bronchoscopy or immunomodulatory medication.
Who cannot join
- 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.
- Bronchoscopy Exclusion criteria (ITU patients):
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Liverpool University Hospital
Liverpool, Merseyside, L7 8XP
About this study
Official title: Using P4 Peptide to Augment Ex Vivo Phagocyte Function in Patients with Severe Community Acquired Pneumonia (CAP)
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).
Read the 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
- a peptide that enhances bacterial uptake and killing by phagocytes.
- 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
- Being tested
- Venepuncture, Bronchoscopy
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenepunctureProcedure or surgery
Taken from established arterial or central lines in critical care setting or by experienced clinicians if no line available and in healthy volunteers.
BronchoscopyProcedure or surgery
Broncho-alveolar lavage to obtain alveolar macrophages
| Study group | Role | What they receive |
|---|---|---|
| ITU patients | 25 patients will be recruited from the Intensive Care Unit/ High dependency unit Inclusion- Adults (>18years) with community acquired pneumonia (CAP). Receives: Procedure: Venepuncture; Procedure: Bronchoscopy | |
| 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. Receives: Procedure: Venepuncture; Procedure: Bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of bacteria phagocytosed from neutrophils and macrophages stimulated with P4 compared to unstimulated cells.comparing cells stimulated with P4 and unstimulated cells.
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.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study startJan 2013
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liverpool University Hospitals NHS Foundation Trust
- Sponsor type
- Other government
- Collaborators
- Liverpool School of Tropical Medicine
- Responsible party
- Sponsor
- Investigators
- Stephen B Gordon, Professor, Principal investigator, Royal Liverpool University Hospital/ Liverpool School of Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03497962
- Sponsor's protocol ID
- 12/NW/0730
- Acronym
- P4
- Status last verified
- May 2017
- First submitted
- 8 May 2015
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using P4 Peptide to Augment Ex Vivo Phagocyte Function in Patients with Severe Community Acquired Pneumonia (CAP)
- ClinicalTrials.gov ID
- NCT03497962
- Acronym / sponsor ID
- P4 / 12/NW/0730
- Conditions
- Pneumonia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Liverpool University Hospitals NHS Foundation TrustOther government
- Collaborators
- Liverpool School of Tropical Medicine
- Study start
- Jan 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 13 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- a peptide that enhances bacterial uptake and killing by phagocytes.
- 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ITU patients | – | Procedure: Venepuncture, Procedure: Bronchoscopy25 patients will be recruited from the Intensive Care Unit/ High dependency unit Inclusion- Adults (>18years) with community acquired pneumonia (CAP). |
| Healthy volunteer | – | Procedure: Venepuncture, Procedure: Bronchoscopy24 healthy adult volunteers will be recruited to establish a comparison data set and to extend the laboratory observations to include other bacterial pathogens. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted into the intensive care unit with community aquired pneumonia (CAP) Healthy volunteer
Key inclusion criteria (8 listed)
- 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.
- Adults (>18y).
- Able to give fully informed consent.
- Fluent English speaker.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenepunctureTaken from established arterial or central lines in critical care setting or by experienced clinicians if no line available and in healthy volunteers. | Procedure or surgery | Healthy volunteer, ITU patients |
| BronchoscopyBroncho-alveolar lavage to obtain alveolar macrophages | Procedure or surgery | Healthy volunteer, ITU patients |
Primary outcome
Number of bacteria phagocytosed from neutrophils and macrophages stimulated with P4 compared to unstimulated cells.comparing cells stimulated with P4 and unstimulated cells.
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen B Gordon, Professor principal investigator
Royal Liverpool University Hospital/ Liverpool School of Tropical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pneumonia, run by Liverpool University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of bacteria phagocytosed from neutrophils and macrophages stimulated with P4 compared to unstimulated cells.comparing cells stimulated with P4 and unstimulated cells. (time frame: 12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.