Sepsis in Oncology Patients

NCT06046677 | Not Yet Recruiting

• 1 other identifier: CCR5669
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this prospective observational study is to address the significant knowledge gap that exists around the impact of immune dysfunction on the development and survival from sepsis in patients with cancer. This proposal primarily focuses on establishing the transcriptomic immune profiles of sepsis patients with a background of cancer. This analysis will be complemented with in vitro functional analyses, and in addition will commence a collection of genome-wide data, including a focus on predicting white cell number and function in health. Uniquely, the investigators propose to establish a robust link between these analyses: transcriptomic, in vitro, and genome-wide, to enable them to comprehensively explore septic oncology patient 'immune phenotypes' and effectively identify novel exploitable therapeutic pathways. To this end, this project will collect, analyse and/or sequence DNA, RNA, leukocytes and soluble materials from a cohort of oncology patients presenting to intensive care with sepsis. This cohort will include all-comers with an oncological background but will also focus on two core groups at high risk of sepsis where baseline samples can also be sought prior to major immunosuppressive events in the cancer pathway. These are:

1. 1.Oesophageal/upper gastrointestinal (GI) cancer patients prior to systemic anticancer therapy initiation or surgery
2. 2.Haematological malignancy patients prior to stem cell transplantation.

Conditions

Sepsis in Cancer Patients

Outcome Measures

Primary Outcomes (2)

• Identification of circulating leukocyte transcriptomic phenotypes relating to mortality in sepsis patients with a background of cancer, (in comparison to those previously identified in non-immunosuppressed patients).

  Identification of circulating leukocyte transcriptomic phenotypes relating to mortality in sepsis patients with a background of cancer, (in comparison to those previously identified in non-immunosuppressed patients).

  end of trial (4 years)

• 28 day mortality

  28 day mortality

  end of recruitment (3 years)

Secondary Outcomes (6)

• Differences in the trajectory of transcriptomic phenotypes of patients admitted to ICU with sepsis, and how they relate to severity scorings and mortality/morbidity outcomes

  end of trial (4 years)

• Differences in the trajectory of functional phenotypes of patients admitted to ICU with sepsis, and how they relate to severity scorings and mortality/morbidity outcomes

  end of trial (4 years)

• Differences in the trajectory of genomic phenotypes of patients admitted to ICU with sepsis, and how they relate to severity scorings and mortality/morbidity outcomes

  end of trial (4 years)

• Identification of differences in transcriptomic phenotypes between patient subgroups and on comparison to non-immunosuppressed sepsis patients. Comparison in length of stay measures and quality of life parameters

  end of trial (4 years)

• Identification of differences in functional phenotypes between patient subgroups and on comparison to non-immunosuppressed sepsis patients. Comparison in length of stay measures and quality of life parameters

  end of trial (4 years)

Study Arms (2)

Sepsis cohort

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction can be identified as an acute change in total SOFA score ≥2 points consequent to the infection.

Other: No intervention

Elective cohort

Elective pre-operative upper GI surgical patients or elective stem cell transplant patients will be consented and enrolled at baseline, immediately prior to these procedures. If they go on to develop sepsis within 60 days of their surgery, they will go on to be sampled as per the sepsis cohort

Other: No intervention

Interventions

No intervention OTHER

No intervention

Elective cohort; Sepsis cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who develop sepsis on ICU or require admission to ICU with sepsis will be identified and screened for enrolment by the research team at the Royal Marsden NHS Foundation Trust Elective pre-operative upper GI surgical patients or elective stem cell transplant patients will be consented and enrolled at baseline, immediately prior to these procedures.

You may qualify if:

• Patients admitted to ICU with a diagnosis of sepsis as per 'Sepsis-3' definitions with a SOFA score \[REF\] ≥2 secondary to infection from any source
• ≥18 years of age
• Written consent from patient, personal or professional consultee, or deferred consent if none of the above available at admission

You may not qualify if:

• Death deemed imminent by the clinical team
• Patients undergoing elective major upper GI surgery (oesophago+/-gastrectomy) or stem cell transplant for haematological malignancy
• ≥18 years of age
• Written consent from patient
• Limitations in place regarding provision of treatment and/or organ support e.g., palliative patients

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (1)

The Royal Marsden NHS Foundation Trust

London, SW36JJ, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Buffy coat \& PMBCs PAXgene RNA Plasma

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: September 21, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)