Respiration DisordersSIPRESNCT06977165
Investigating the Impact of Sepsis Phenotypes on Antibiotic Treatment in Patients With Severe Pneumonia and Sepsis
An observational study of Respiration Disorders and Respiratory Failure, run by University of Manchester at 1 site in United Kingdom.
Trial summary
Aim of the research: To find out why antibiotics work differently in certain patients with severe pneumonia and sepsis. Background: Individuals can become very unwell from pneumonia, sometimes requiring admission to hospital or even the intensive care unit (ICU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiration Disorders, Respiratory Failure, Sepsis
- What is being tested?
- Antibiotic quantification
- How many people
- 119 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2025to 30 Sep 2027
- Phase
- Observational
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
- No healthy volunteers
- Adult, Older adult
Study population: Hospitalised critically ill patients admitted to the intensive care unit
Who may be able to join
- age ≥ 18 years;
- admitted to intensive care and receiving at least one-organ supportive care;
- treated for presumed or confirmed lower respiratory infection;
- receiving or about to receive piperacillin/tazobactam as part of standard clinical care;
- valid informed consent or enrolment through deferred consent pathway appropriate.
Who cannot join
- unlikely to survive 24 hours as judged by the treating physician;
- study antimicrobial started more than 24 hours prior.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
The University of Manchester
Manchester, Lancashire, M13 9PL
Jan Hansel, MD MRes, +44 161 275 1319, jan.hansel@manchester.ac.uk
About this study
Official title: Investigating the Impact of Sepsis Phenotypes on Antibiotic Treatment in Patients With Severe Pneumonia and Sepsis: a Prospective Observational Cohort Study
Aim of the research: To find out why antibiotics work differently in certain patients with severe pneumonia and sepsis.
Background: Individuals can become very unwell from pneumonia, sometimes requiring admission to hospital or even the intensive care unit (ICU). In some cases, pneumonia can lead to a condition called sepsis, which can be deadly if not treated quickly. In the UK, approximately 30,000 patients die from pneumonia every year. Clinicians use antibiotic injections to treat life-threatening infections such as severe pneumonia. After being injected into the bloodstream, antibiotics quickly spread throughout the body, attacking the infection. Antibiotics are eventually broken down and removed from the body by the kidneys and other organs. However, antibiotics fail to achieve the same consistent result for every patient. This may be to do with the way the antibiotics travel through and are removed from the body, leading to different antibiotic levels in the blood at any one time. Low antibiotic levels can result in worse outcomes and antibiotic resistance. Patients can be grouped based on how their immune system reacts to infections. The SIPRES Study aims to explore if these previously described groups explain the difference in antibiotic levels in patients with severe pneumonia and sepsis.
Read more
Procedures: We will study how adult patients with severe pneumonia respond when treated with the most commonly used antibiotic in the ICU called piperacillin/tazobactam. Alongside information on how quickly patients get better and how long they need to stay in hospital or in ICU, we will collect blood samples to measure antibiotic levels and assess each patient's immune system at two time points during their treatment. This will allow us to measure antibiotic levels in blood at different times and group patients based on their immune system reaction to infection. We will describe the range of antibiotic levels seen in the different immune system reaction groups using mathematical and statistical models.
Patient involvement: We are working closely with people who have experienced severe pneumonia and will work with two patient partners and a patient advisory group to help shape this research. Patient contributors have already shaped the development of the funding application and identified important study outcomes. Patients we have spoken to are concerned over the appropriate dosing of antibiotics and appreciate the need for improved and precise approaches to treating severe infections. Moving forward, patient partners will help finalise the protocol, develop patient and public facing materials, provide their perspective on the study results and shape plans to share the outcomes of the study more broadly.
Potential impact: The SIPRES Study will help identify a group of patients at risk of low antibiotic levels in blood, who are less likely to improve with treatment and more likely to develop antibiotic resistance. Mathematical models that can help clinicians personalise antibiotic dosing for each critically ill patient with severe pneumonia will be developed. Findings have the potential to limit the development of antibiotic resistance and help patients survive and get better faster so that they can return to their normal daily lives. Individualised dosing for patients with low antibiotic levels, as opposed to 'one size fits all' prescribing, also has the potential to more efficiently allocate scarce resources to those who will benefit the most.
- Conditions
- Respiration Disorders, Respiratory Failure, Sepsis, Infection in ICU, Pneumonia
- Being tested
- Antibiotic quantification
- Keywords
- sepsis, pneumonia, therapeutic drug monitoring, beta-lactam antibiotics, piperacillin-tazobactam
- Medical subject headings
- Respiration Disorders, Respiratory Insufficiency, Sepsis, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antibiotic quantificationDiagnostic test
Piperacillin/tazobactam quantification using liquid chromatography-tandem mass spectrometry
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum concentrations of antimicrobial
The primary outcome of serum concentrations of antimicrobials was chosen to assess the profile of medication processing in the body between the groups of interest. Multiple blood samples are taken over the space of one dosing interval (most often 6-8 hours for piperacillin/tazobactam), which allows the calculation of an area under the concentration curve over time. For participants who remain in ICU at Visit 2 (Day 3-5) and are still receiving antimicrobials, a second sampling episode will occur. Those discharged from ICU prior will undergo only a single sampling period.
Measured: Day 0 ± Day 3-5
Secondary outcomes (13)
Baseline Sequential Organ Failure Assessment score (SOFA)
SOFA score at baseline
Measured: Day 0
Change in SOFA score
Difference between aggregate SOFA scores
Measured: From Day 0 to Day 3-5
All-cause mortality
Death censored at Day 28
Measured: At Day 28
Days alive and out of hospital
Defined as the number of days not in hospital at Day 28
Measured: At Day 28
Hospital and ICU length of stay
Number of days in hospital/ICU
Measured: At Day 28
Clinical cure
Defined as the completion of antibiotic treatment course (on or prior to Day 28) without recommencement of antibiotic therapy within 48 hours of cessation
Measured: At Day 28
Microbiological cure
Defined as at least two negative cultures following proven bacterial infection and no new positive cultures at Day 28
Measured: At Day 28
Duration of primary course of antimicrobial treatment
Number of days of treatment with antimicrobial from baseline
Measured: At Day 28
Isolated pathogens
Proportion of participants with isolated pathogens
Measured: At Day 28
Emergence of resistant organisms
Any organism resistant to antimicrobials identified through culture from any source (blood, urine, sputum, stool)
Measured: At Day 28
Therapeutic target attainment
100% fraction of the time (fT) above the minimal inhibitory concentration [MIC] 100% fraction of the time (fT) above four times the minimal inhibitory concentration [4xMIC] Assessed for Pseudomonas aeruginosa according to latest EUCAST ECOFF breakpoints at time of analysis
Measured: At Day 0 ± Day 3-5
Immune signature
Phenotype category according to Davenport and Sinha classification
Measured: At Day 0 ± Day 3-5
Safety and toxicity outcomes
Any serious adverse events reported during the study period
Measured: At Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2025
- Study start1 Sep 2025 (estimated)
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiration DisordersStudies 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
- 119 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06977165
- Sponsor's protocol ID
- R131285
- Other IDs
- NIHR304654
- Acronym
- SIPRES
- Status last verified
- May 2025
- First submitted
- 8 May 2025
- Last updated
- 18 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The following anonymised data will be shared on an online accessible repository in line with Findability, Accessibility, Interoperability, and Reuse (FAIR) principles: * Baseline clinical characteristics without identifiable data * Outcome data * Pharmacokinetic data * Transcriptomic data * Immune cytokine data