Clinical trial NCT05052203: Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
Official title: Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis (REQOVERY)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Infection
Keywords: Post sepsis syndrome
Epigenetic
Transcriptome
Recovery
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2021-09-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients between 18-85 years old admitted to the emergency department (ED) of the University Medical Center Groningen (UMCG) with suspected sepsis according to the sepsis-3 criteria who survive their ED admission at three months. A control group will compose of age and sex-matched ED patients admitted for non-infectious causes. Both the septic patients and controls have already been enrolled in the Acutelines study.

Brief summary: Sepsis is a life-threatening dysregulated immune response to infection associated with multi-organ failure and a high mortality rate.While researchers have focused mainly on acute sepsis, post-sepsis care of survivors has long been neglected despite the observation that many sepsis survivors suffer from debilitating post-sepsis syndrome. This syndrome is characterized by frequent hospital readmissions and increased mortality due to persistent immune dysfunction, cardiovascular disease, and cognitive impairment, causing poor quality of life and a substantial burden on the healthcare system. Disconcertingly, the number of sepsis survivors at risk for hospital readmission continues to rise.7 Of the post-sepsis symptoms, post-sepsis immunosuppression is perhaps the most clinically important. While sepsis presents as an initial phase of hyperinflammation (a "cytokine storm"), it is followed by an immunosuppressive phase that is now understood to last weeks to months and predisposes survivors to lethal secondary infections and sepsis recurrence. A third of deaths eight years post-sepsis are caused by recurrent sepsis.We hypothesize that changes in the transcriptome and DNA methylome in immune cells of survivors might be the underlying driver for prolonged immunosuppression, and may also be correlated with long-term morbidity and mortality post-sepsis, as well as other symptoms of post-sepsis syndrome including PTSD and cardiovascular disease.


Eligibility criteria: Inclusion criteria sepsis group:

* Adult patients, aged between 18 and 85 years
* Able to provide informed consent themselves or informed consent can be obtained via next of kin or legal guardian
* Included in Acutelines, where blood sample was drawn upon ED admission
* Satisfy the Sepsis-3 criteria for sepsis (Figure 2), combined with clinical suspicion of infection and/or fever (body temperature \> 38.5°C)
* Survive at 3 months post discharge
* Inclusion criteria control group:Adult patients, aged between 18 and 85 years
* Able to provide informed consent themselves or informed consent can be obtained via next of kin or legal guardian
* Included in Acutelines, where blood sample was drawn upon ED admission
* Non-infectious reason of admission (specifically syncope, electrolyte disturbance, intoxication, gastro-intestinal bleeding)

4.3 Exclusion criteria

The participants should not meet any of the following exclusion criteria:

* Transfer from another hospital
* Emergency room visit in connection with accidental exposure of bodily material to patient ("needle stick injury")
* Visit an emergency room in connection with organ transplantation
* Discharged home without hospital admittance after ED visit
* Unable to give blood
* Immunosuppressive therapies such as corticosteroids (\>10mg) or small molecule immune suppressants within the last three months, or biologicals administered within the last year
* Radiotherapy or systemic chemotherapy within the last three months
* Known pregnancy; the presence of pregnancy will be verified by asking the potential participant
* A hospitalization of more than 21 days

Primary outcomes:
measure: DNA methylation (epigenetics) using the Illumina MethylationEPIC kit. Changes in DNA methylation at gene promoter/enhancer sites will be correlated through the NetworkAnalyst platform.
timeFrame: baseline versus 3 months follow up
measure: Gene expression (transcriptomics/qPCR) will be measured using the Illumina Hi-Seq instrument. Differential gene expression will be correlated through the NetworkAnalyst platform.
timeFrame: baseline versus 3 months follow up
Secondary outcomes:
measure: Nutrition status measured with PS-SGA Short Form and SNAQ form. (both questionnaires)
timeFrame: 3 months
measure: Mortality. Mortality status will be obtained from the Municipal Personal Records Database (BRP), containing reliable and complete registration all Dutch citizens
timeFrame: 1 year
measure: Demographics
timeFrame: 3 months
measure: Intoxications
timeFrame: 3 months
measure: Medication use
timeFrame: 3 months
measure: Sepsis severity defined with SOFA score
timeFrame: 3 months follow up
measure: Fatigue assessed with piper fatigue scale
timeFrame: 3 months
measure: Mood assessed with the Patient Health Questionnaire-2 ( (questionnaire)
timeFrame: 3 months
measure: Somatic symptoms (e.g. Patient Health questionnaire-15)
timeFrame: 3 months
measure: Activities of daily living as determined by EQ-5D-5L (if abnormal also Katz-ADL-6)
timeFrame: 3 months
measure: Physical activity (e.g. Short Questionnaire to Assess Health-Enhancing Activity) (SQUASH) and 'Utrechtse activiteiten lijst' (UAL))
timeFrame: 3 months
measure: Co-morbidity (a.o. Charlson comorbidity index)
timeFrame: 3 months
measure: Vital parameters
timeFrame: At baseline and three months.
measure: Length-of-stay in hospital/intensive care unit (ICU)
timeFrame: 0-3 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References: