SepsisHEAL-SEPSISNCT07273344
A Study on How the Immune System Responds to Sepsis and Its Long-term Effects
An observational study of Sepsis, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Sepsis occurs when an infection, caused by bacteria, a virus, or a fungus, enters the body and throws the immune system out of balance. Instead of protecting the body, the immune response may become too strong and start damaging healthy organs, or it may become too weak and fail to control the infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- blood sampling
- How many people
- 400 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 Nov 2025to 1 Dec 2028
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: ICU or medium care patients diagnosed with sepsis, as defined by the Sepsis-3 criteria, from the Radboudumc, Canisius Wilhelmina Ziekenhuis, Rijnstate Ziekenhuis, Jeroen Bosch Ziekenhuis, Gelre Ziekenhuis Apeldoorn, Catharina Ziekenhuis or Slingeland Ziekenhuis.
Who may be able to join
- Adults (≥18years).
- Sepsis 3 criteria: defined as having a suspected or documented infection accompanied by organ dysfunction, represented by a total Sequential Organ Failure Assessment (SOFA-2) score 2 or more for new admissions or as 2 or more point-increase of the total SOFA-2 score for hospitalized patients.
Who cannot join
- Known chemotherapy-induced or long-term neutropenia.
- Known CD4 counts <400 cells/µL.
- History of primary immunodeficiency
- Chronic intake of corticosteroids (defined as total daily dose equal or greater than 0.4 mg/kg of equivalent prednisone for more than the last 15 days).
- Current use of biologics.
- Solid organ transplant recipients.
- Recipients of allogeneic bone marrow transplants.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Wouter A. van der Heijden, dr. contact
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Center
Nijmegen, Gelderland
Tristan Couwenbergh, +31243618819, tristan.couwenbergh@radboudumc.nl
About this study
Official title: A Systems Immunology Approach to Characterize the Immune Response in Sepsis and Its Long-term Complications
Sepsis occurs when an infection, caused by bacteria, a virus, or a fungus, enters the body and throws the immune system out of balance. Instead of protecting the body, the immune response may become too strong and start damaging healthy organs, or it may become too weak and fail to control the infection. Both situations can be life-threatening. Even people who survive sepsis may experience long-term health problems, such as new infections, heart and blood vessel diseases, or early death.
This study aims to better understand how the immune system behaves during and after sepsis. We believe that there are different types of immune responses in sepsis, called immunotypes. We will identify these immunotypes by examining substances in the blood and changes in immune cells. We will then study which immunotypes help protect patients and which may cause short- or long-term harm.
Read more
Understanding these immunotypes may make it possible in the future to quickly determine what type of immune response a patient with sepsis has. This could help doctors choose the best treatment for each individual patient.
A total of 400 patients with sepsis from the intensive care unit will take part in this study. We will collect blood samples at several time points and gather information about their health. Participants will be followed from their intensive care admission until one year after they return home.
Read the detailed description
Sepsis is a life-threatening organ failure syndrome caused by a dysregulated host response to infection. Despite advances in antimicrobial therapy and intensive care, mortality remains high due to our inability to rebalance the host immune response. Current immunotherapy strategies fail to account for the highly heterogeneous immunopathological mechanisms underlying sepsis. Some patients experience hyperinflammation, others immune paralysis, with these states often coexisting or shifting over time. Moreover, different immunological mechanisms may drive each of these broad patterns of immune dysregulation. Defining patient immunotypes and identifying associated biomarkers is therefore essential for developing targeted immunotherapies. Additionally, the long-term morbidity and mortality following sepsis, potentially driven by lasting epigenetic changes, are poorly understood. A deeper understanding of immunotypes and their impact on both acute and long-term outcomes is essential to improve patient stratification and guide future precision medicine approaches in sepsis.
This study aims to characterize sepsis immunotypes linked to short- and long-term outcomes and identify novel biomarkers and therapeutic targets. This is a multicenter, prospective, observational cohort study. We aim to recruit a cohort of 400 intensive care or medium care patients diagnosed with sepsis, as defined by the Sepsis-3 criteria. No randomization will be performed. Blood samples and clinical data will be collected on the following timepoints: day 0 (within 48 hours of ICU/MC admission), day 3 (±1 day, defined as 3 days after day 0), at hospital discharge (±2 days), and at 3 and 12 months post-discharge (each ±2 weeks). Patients will be retrospectively classified into subgroups according to infection site, as defined by the International Sepsis Forum Consensus Conference definitions. This study involves no interventions beyond scheduled blood collection. The amount of blood drawn at each timepoint will not exceed 40 ml. To minimize additional venipunctures during admission, blood collection will be incorporated into routine clinical care whenever possible. Clinical data at 3 and 12 months post-discharge will be gathered through questionnaires or phone interviews. The only additional travel required for the study is for post-discharge blood collection, which participants can choose to complete at an external Radboudumc-affiliated blood collection site closest to their home. Therefore, for all patients, including those who may be incapacitated during the acute phase of sepsis, the risks and burden associated with participation are considered minimal. Patients will not receive any direct benefit from participating in this study. However, the knowledge gained is expected to guide future sepsis diagnoses, treatment and prediction of health outcomes.
- Conditions
- Sepsis
- Being tested
- blood sampling
- Keywords
- observational, sepsis, cohort study, immune endotypes, endotypes, immunotypes, post-sepsis syndrome
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingOther
This study involves no interventions beyond scheduled blood collection.
What is being measured
The primary outcome is the main question the study is designed to answer.
Classification of hospitalized sepsis patients into distinct immunotypes.
Measured: Day 0 (within 48 hours of intensive care unit admission or start of sepsis)
Classification of hospitalized sepsis patients into distinct immunotypes.
Measured: Day 3 (defined as 3 days after day 0)
Classification of hospitalized sepsis patients into distinct immunotypes.
Measured: At hospital discharge.
Secondary outcomes (2)
Detection of persistent immunotypes at following hospital discharge.
Measured: Three months after hospital discharge.
Detection of persistent immunotypes at following hospital discharge.
Measured: Twelve months after hospital discharge.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2025
- Study start3 Nov 2025
- Primary completion1 Nov 2028 (estimated)
- Study completion1 Dec 2028 (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.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- 400 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Dutch Research Council (NWO)
- Responsible party
- Sponsor
- Investigators
- Mihai G. Netea, Prof. dr., Study director, Radboud University Medical CenterWouter A. van der Heijden, dr., Principal investigator, Radboud University Medical CenterPeter Pickkers, Prof. dr., Study director, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07273344
- Sponsor's protocol ID
- NL010169
- Acronym
- HEAL-SEPSIS
- Status last verified
- Nov 2025
- First submitted
- 14 Nov 2025
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The HEAL-SEPSIS project will share all pseudonymized IPD used in analyses and publications under restricted access, in accordance with participant consent and intellectual property protections. Privacy and confidentiality obligations prevent unrestricted sharing of full IPD datasets
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Systems Immunology Approach to Characterize the Immune Response in Sepsis and Its Long-term Complications
- ClinicalTrials.gov ID
- NCT07273344
- Acronym / sponsor ID
- HEAL-SEPSIS / NL010169
- Conditions
- Sepsis
- Keywords
- observational, sepsis, cohort study, immune endotypes, endotypes, immunotypes, post-sepsis syndrome
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- The Dutch Research Council (NWO)
- Study start
- 3 Nov 2025 (actual)
- Primary completion
- 1 Nov 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 9 Dec 2025 (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 occurs when an infection, caused by bacteria, a virus, or a fungus, enters the body and throws the immune system out of balance. Instead of protecting the body, the immune response may become too strong and start damaging healthy organs, or it may become too weak and fail to control the infection. Both situations can be life-threatening. Even people who survive sepsis may experience long-term health problems, such as new infections, heart and blood vessel diseases, or early death.
This study aims to better understand how the immune system behaves during and after sepsis. We believe that there are different types of immune responses in sepsis, called immunotypes. We will identify these immunotypes by examining substances in the blood and changes in immune cells. We will then study which immunotypes help protect patients and which may cause short- or long-term harm.
Understanding these immunotypes may make it possible in the future to quickly determine what type of immune response a patient with sepsis has. This could help doctors choose the best treatment for each individual patient.
A total of 400 patients with sepsis from the intensive care unit will take part in this study. We will collect blood samples at several time points and gather information about their health. Participants will be followed from their intensive care admission until one year after they return home.
Detailed description
Sepsis is a life-threatening organ failure syndrome caused by a dysregulated host response to infection. Despite advances in antimicrobial therapy and intensive care, mortality remains high due to our inability to rebalance the host immune response. Current immunotherapy strategies fail to account for the highly heterogeneous immunopathological mechanisms underlying sepsis. Some patients experience hyperinflammation, others immune paralysis, with these states often coexisting or shifting over time. Moreover, different immunological mechanisms may drive each of these broad patterns of immune dysregulation. Defining patient immunotypes and identifying associated biomarkers is therefore essential for developing targeted immunotherapies. Additionally, the long-term morbidity and mortality following sepsis, potentially driven by lasting epigenetic changes, are poorly understood. A deeper understanding of immunotypes and their impact on both acute and long-term outcomes is essential to improve patient stratification and guide future precision medicine approaches in sepsis.
This study aims to characterize sepsis immunotypes linked to short- and long-term outcomes and identify novel biomarkers and therapeutic targets. This is a multicenter, prospective, observational cohort study. We aim to recruit a cohort of 400 intensive care or medium care patients diagnosed with sepsis, as defined by the Sepsis-3 criteria. No randomization will be performed. Blood samples and clinical data will be collected on the following timepoints: day 0 (within 48 hours of ICU/MC admission), day 3 (±1 day, defined as 3 days after day 0), at hospital discharge (±2 days), and at 3 and 12 months post-discharge (each ±2 weeks). Patients will be retrospectively classified into subgroups according to infection site, as defined by the International Sepsis Forum Consensus Conference definitions. This study involves no interventions beyond scheduled blood collection. The amount of blood drawn at each timepoint will not exceed 40 ml. To minimize additional venipunctures during admission, blood collection will be incorporated into routine clinical care whenever possible. Clinical data at 3 and 12 months post-discharge will be gathered through questionnaires or phone interviews. The only additional travel required for the study is for post-discharge blood collection, which participants can choose to complete at an external Radboudumc-affiliated blood collection site closest to their home. Therefore, for all patients, including those who may be incapacitated during the acute phase of sepsis, the risks and burden associated with participation are considered minimal. Patients will not receive any direct benefit from participating in this study. However, the knowledge gained is expected to guide future sepsis diagnoses, treatment and prediction of health outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- ICU or medium care patients diagnosed with sepsis, as defined by the Sepsis-3 criteria, from the Radboudumc, Canisius Wilhelmina Ziekenhuis, Rijnstate Ziekenhuis, Jeroen Bosch Ziekenhuis, Gelre Ziekenhuis Apeldoorn, Catharina Ziekenhuis or Slingeland Ziekenhuis.
Key inclusion criteria (2 listed)
- Adults (≥18years).
- Sepsis 3 criteria: defined as having a suspected or documented infection accompanied by organ dysfunction, represented by a total Sequential Organ Failure Assessment (SOFA-2) score 2 or more for new admissions or as 2 or more point-increase of the total SOFA-2 score for hospitalized patients.
Key exclusion criteria (7 listed)
- Known chemotherapy-induced or long-term neutropenia.
- Known CD4 counts <400 cells/µL.
- History of primary immunodeficiency
- Chronic intake of corticosteroids (defined as total daily dose equal or greater than 0.4 mg/kg of equivalent prednisone for more than the last 15 days).
- Current use of biologics.
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 |
|---|---|---|
| blood samplingThis study involves no interventions beyond scheduled blood collection. | Other | – |
Primary outcome
Classification of hospitalized sepsis patients into distinct immunotypes.
Time frame: Day 0 (within 48 hours of intensive care unit admission or start of sepsis)
Classification of hospitalized sepsis patients into distinct immunotypes.
Time frame: Day 3 (defined as 3 days after day 0)
Classification of hospitalized sepsis patients into distinct immunotypes.
Time frame: At hospital discharge.
2 secondary outcomes
Detection of persistent immunotypes at following hospital discharge.
Time frame: Three months after hospital discharge.
Detection of persistent immunotypes at following hospital discharge.
Time frame: Twelve months after hospital discharge.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- Individual participant dataSharing planned: Yes. The HEAL-SEPSIS project will share all pseudonymized IPD used in analyses and publications under restricted access, in accordance with participant consent and intellectual property protections. Privacy and confidentiality obligations prevent unrestricted sharing of full IPD datasets
Related trials for Sepsis
Not yet recruitingObservational study
Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis
Sepsis, Septic Shock
RecruitingPhase 3
A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
Septic Shock
RecruitingObservational study
Middle East Study of Infections in Patients With Hematological Malignancies
Hematological Malignancy, Hematopoetic Stem Cell Transplantation
RecruitingObservational study
Early Detection and Kinetics of Sepsis-Induced Coagulopathy in Severe Burn Patients
Peer Bullying Intervention, Vodcast
Not yet recruitingObservational study
Comparative Study of the Genomic Characteristics of Uropathogenic Escherichia Coli According to the Severity of Community-Acquired Urinary Tract Infections in Guadeloupe (COLIGENURI)
Urinary Tract Infections
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.
Wouter A. van der Heijden, dr. contact
Mihai G. Netea, Prof. dr. study director
Radboud University Medical Center
Wouter A. van der Heijden, dr. principal investigator
Radboud University Medical Center
Peter Pickkers, Prof. dr. study director
Radboud University Medical Center
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, run by Radboud University Medical Center 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 2 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 14 Aug 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tristan Couwenbergh (+31243618819, tristan.couwenbergh@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Classification of hospitalized sepsis patients into distinct immunotypes. (time frame: Day 0 (within 48 hours of intensive care unit admission or start of sepsis)). The study lists 3 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 14 Aug 2026.