SepsisREQOVERYNCT05052203
Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
An observational study of Sepsis and Infection, run by Hjalmar Bouma at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- What is being tested?
- Exposure of interest: study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytes
- How many people
- 120 participants
- Where
- 1 siteNetherlands
- Study dates
- 28 Sep 2021to Dec 2023
- 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 to 85 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 20Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis (REQOVERY)
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.
- Being tested
- Exposure of interest: study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytes
- Keywords
- Post sepsis syndrome, Epigenetic, Transcriptome, Recovery
- Medical subject headings
- Sepsis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure of interest: study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytesOther
The primary objective is to study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation (epigenetics) using the Illumina MethylationEPIC kit. Changes in DNA methylation at gene promoter/enhancer sites will be correlated through the NetworkAnalyst platform.
The primary objective of the current project is to measure changes in DNA methylation (i.e. epigenetics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge.
Measured: baseline versus 3 months follow up
Gene expression (transcriptomics/qPCR) will be measured using the Illumina Hi-Seq instrument. Differential gene expression will be correlated through the NetworkAnalyst platform.
The primary objective of the current project is to measure changes in gene expression (i.e. transcriptomics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge.
Measured: baseline versus 3 months follow up
Secondary outcomes (14)
Nutrition status measured with PS-SGA Short Form and SNAQ form. (both questionnaires)
study the association between epigenetic and transcriptomic signatures in sepsis and survivors with nutrition status. PS-SGA short form looks at weight loss, upper arm circumference, apetite and functionallity. PS-SGA short form scores weight, food intake, symptoms, activities and functionalilyti (nummeric; 0-52).
Measured: 3 months
Mortality. Mortality status will be obtained from the Municipal Personal Records Database (BRP), containing reliable and complete registration all Dutch citizens
study the association between epigenetic and transcriptomic signatures and mortality in sepsis survivors and non-survivors and healthy controls. Mortality will be retrieved from the electronic health records (EHR) from the hospital and municipal registration. The cause of death will be retrieved from the EHR from the hospital, general practitioner and Dutch statistics' office (CBS).
Measured: 1 year
Demographics
To study the association between epigenetic and transcriptomic signatures in sepsis survivors with demographics. Information about demograpics will be retrieved from the electronic health records (EHR) from the hospital.
Measured: 3 months
Intoxications
To study the association between epigenetic and transcriptomic signatures in sepsis survivors with intoxications. Information about intoxications will be retrieved from the electronic health records (EHR) from the hospital.
Measured: 3 months
Medication use
To study the association between epigenetic and transcriptomic signatures in sepsis survivors with medication use. Medication use will be retrieved from the electronic health records (EHR) from the hospital, general practitioner and pharmacy.
Measured: 3 months
Sepsis severity defined with SOFA score
study the association between severity of sepsis and the epigenetic and transcriptomic signatures in sepsis. SOFA scores will be available for patients admitted because of an infection.
Measured: 3 months follow up
Fatigue assessed with piper fatigue scale
To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with fatigue.Piper Fatigue Scale-12 (PFS-12; 0-10, higher scores reflect more fatigue among four subscales (a) behavior, (b) affect, (c) sensory, (d) cognition)
Measured: 3 months
Mood assessed with the Patient Health Questionnaire-2 ( (questionnaire)
To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with mood. Patient Health Questionnaire-2 (PHQ-2; 0-6, higher score corresponds to reduced mental health)
Measured: 3 months
Somatic symptoms (e.g. Patient Health questionnaire-15)
To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with somatic symptoms. Patient Health Questionnaire-15 (PHQ-15; 0-30, minimal-high somatic symptom severity)
Measured: 3 months
Activities of daily living as determined by EQ-5D-5L (if abnormal also Katz-ADL-6)
To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with activities of daily living. EuroQol-5D (EQ5D; simple descriptive profile and a single index value for health status; higher values corresponding with better health) with visual analogue scale (VAS; 0-100, worse-best experienced health). Katz ADL-6 (0-6, fully dependent-independent)
Measured: 3 months
Physical activity (e.g. Short Questionnaire to Assess Health-Enhancing Activity) (SQUASH) and 'Utrechtse activiteiten lijst' (UAL))
To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with physical activity
Measured: 3 months
Co-morbidity (a.o. Charlson comorbidity index)
To study the association between epigenetic and transcriptomic signatures in sepsis and survivors with comorbidity. Co-morbidity will be retrieved from the electronic health records (EHR) from the hospital, general practitioner and pharmacy. Data will be registered according to the Charlson' co-morbidity index (CCI; 1-2 mild co-morbidity, 3-4 moderate co-morbidity, 5 severe co-morbidity)
Measured: 3 months
Vital parameters
Heart rate (bpm), blood pressure (mmHg), oxygen saturation (SpO2, SaO2, PaO2), breathing frequency (per min), consciousness (Glasgow coma scale), pain score (VAS), nausea/vomiting (y/n), defecation (y/n), urination (y/n), body weight (kg), length (cm), fluid balance (ml/day).
Measured: At baseline and three months.
Length-of-stay in hospital/intensive care unit (ICU)
Length-of-stay in hospital and on intensive care unit (ICU) in days
Measured: 0-3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2021
- Study start28 Sep 2021
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies 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
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hjalmar Bouma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hjalmar Bouma, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05052203
- Sponsor's protocol ID
- 202100108
- Acronym
- REQOVERY
- Status last verified
- May 2023
- First submitted
- 27 Aug 2021
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis (REQOVERY)
- ClinicalTrials.gov ID
- NCT05052203
- Acronym / sponsor ID
- REQOVERY / 202100108
- Keywords
- Post sepsis syndrome, Epigenetic, Transcriptome, Recovery
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Hjalmar BoumaUniversity, hospital or other
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 22 Sep 2021 (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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Exposure of interest: study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytesThe primary objective is to study DNA methylation (epigenetics) and gene expression (transcriptomics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge | Other | – |
Primary outcome
DNA methylation (epigenetics) using the Illumina MethylationEPIC kit. Changes in DNA methylation at gene promoter/enhancer sites will be correlated through the NetworkAnalyst platform.
Time frame: baseline versus 3 months follow up
The primary objective of the current project is to measure changes in DNA methylation (i.e. epigenetics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge.
Gene expression (transcriptomics/qPCR) will be measured using the Illumina Hi-Seq instrument. Differential gene expression will be correlated through the NetworkAnalyst platform.
Time frame: baseline versus 3 months follow up
The primary objective of the current project is to measure changes in gene expression (i.e. transcriptomics) of blood leukocytes between sepsis survivors at ED admission and three months after hospital discharge.
14 secondary outcomes
Nutrition status measured with PS-SGA Short Form and SNAQ form. (both questionnaires)
Time frame: 3 months
Mortality. Mortality status will be obtained from the Municipal Personal Records Database (BRP), containing reliable and complete registration all Dutch citizens
Time frame: 1 year
Demographics
Time frame: 3 months
Intoxications
Time frame: 3 months
Medication use
Time frame: 3 months
Sepsis severity defined with SOFA score
Time frame: 3 months follow up
Fatigue assessed with piper fatigue scale
Time frame: 3 months
Mood assessed with the Patient Health Questionnaire-2 ( (questionnaire)
Time frame: 3 months
Somatic symptoms (e.g. Patient Health questionnaire-15)
Time frame: 3 months
Activities of daily living as determined by EQ-5D-5L (if abnormal also Katz-ADL-6)
Time frame: 3 months
Physical activity (e.g. Short Questionnaire to Assess Health-Enhancing Activity) (SQUASH) and 'Utrechtse activiteiten lijst' (UAL))
Time frame: 3 months
Co-morbidity (a.o. Charlson comorbidity index)
Time frame: 3 months
Vital parameters
Time frame: At baseline and three months.
Length-of-stay in hospital/intensive care unit (ICU)
Time frame: 0-3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Sepsis and Infection, run by Hjalmar Bouma at 1 site in Netherlands.
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 20 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 10 May 2023. 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 Netherlands. 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?
Results are not available in the source record.
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?
DNA methylation (epigenetics) using the Illumina MethylationEPIC kit. Changes in DNA methylation at gene promoter/enhancer sites will be correlated through the NetworkAnalyst platform. (time frame: baseline versus 3 months follow up). The study lists 2 primary outcomes in all. 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 10 May 2023.