SepsisMARS-IndiaNCT03727243
Molecular Diagnosis and Risk Stratification of Sepsis in India
An observational study of Sepsis and Septic Shock, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in India.
Trial summary
Background: Globally, sepsis is common with an estimated population incidence of 437 cases per 100, 000 person-years and acute mortality of 26%, one of the few major medical conditions whose incidence and resulting mortality continues to rise. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Septic Shock, Sepsis Syndrome
- How many people
- 550 participants
- Where
- 1 siteIndia
- Study dates
- 6 Dec 2018to 11 Jun 2021
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients hospitalised in the general, emergency and neuro ICU's of Kasturba Hospital, Manipal. KMC hospital is a >2000 bedded tertiary care hospital that treats patients from a wide geographic area which can sometimes stretch beyond the state of Karnataka itself. Most patients will be from a mixture of urban and rural settings, with tropical infectious presentations varying throughout the year.
Who may be able to join
- All patients aged 18 years and over in the intensive care units of Kasturba Hospital, Manipal (and meeting the study population definitions below)
- Sepsis - defined as the presence of infection diagnosed within 24 hours of ICU admission with probable or definite likelihood, accompanied by organ dysfunction represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. Septic shock is defined as per the recent Sepsis 3.0 consensus guidelines.
- Serious trauma within 24 hours, with patient directly admitted to ICU (injury severity score (ISS) >15).
- Severe burns (total surface area burned >30%).
- Major surgery or pancreatitis/non-infectious inflammation.
Who cannot join
- Pregnant or breast-feeding women
- Patients with a 'withdrawal of care' decision at time of inclusion
- Patients whose anticipated duration of hospitalisation in ICU is estimated <48 hours
- Extra-corporeal circulation in the month preceding inclusion in the case of cardiac surgery
- Patient with restricted liberty or under legal protection
- Expected lifespan <3 months due to pre-existing comorbidities
Show all 9Show fewer
- Blood transfusion >4 units in past week
- Second admission to ICU or previous enrolment in study (within same hospital admission)
- Transfer from other hospital ICU (if greater than 24hrs in total)
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Kasturba Hospital, Kasturba Medical College (KMC), Manipal Academy of Higher Education (MAHE)
Udupi, Karnataka, 576104
Chiranjay Mukhopadhyay, MD, PhD, +918202922717, chiranjay.m@manipal.edu
Harjeet Singh Virk, MD, +918202922717, h.s.virk@amc.uva.nl
About this study
Background: Globally, sepsis is common with an estimated population incidence of 437 cases per 100, 000 person-years and acute mortality of 26%, one of the few major medical conditions whose incidence and resulting mortality continues to rise. However, true burden is likely significantly higher as a recent meta- analysis could find no data from LMIC where 87% of the world's population resides.
Objective: Generate new knowledge that will eventually provide rapid and accurate information about an individual patient suffering from sepsis (or critical illness), including which type of microorganism is responsible for the infection and the severity and stage of the patient's immune response.
Methods: MARS-India will be a prospective longitudinal, single-centre observational study, conducted in mixed ICU's of a >2000 bedded tertiary teaching hospital in Manipal, India. The investigators will recruit to three groups- sex and age-matched healthy volunteers (n=150) and patients diagnosed with sepsis/septic shock or non-infectious ICU admissions such as severe trauma, severe burns and patients admitted to ICU after major surgery (n=400). The investigators have optimised a workflow to follow and describe the immunoinflammatory status of septic patients (as well as severe trauma/burn and major surgery) during the first 6 months after their initial injury. At fixed time points the investigators will collect blood in PaxGene, heparin, citrate and EDTA tubes in addition to routine bloods and microbiological samples. Rectal swabs and stool will also be taken for microbiome analysis. Immune functional tests will be performed to determine whole-blood cytokine/chemokine production in response to ex-vivo stimulation using an 8-panel assay. Additionally, complete immunophenotyping using flow cytometry including HLA-DR expression and lymphocyte subsets will be obtained.
Read the detailed description
New sepsis 3.0 definition has for the first time included a dysregulated host response to infection as the cause of organ dysfunction, however, sepsis remains a highly heterogeneous syndrome without an accepted definition of what constitutes a dysregulated host response. The field is only now realising that inclusion of specific characteristics of the host response (transcriptomic or immunological profiles) facilitate stratification of patients with sepsis into subgroups (endotypes), allowing for prognostic enrichment and targeted therapeutic intervention.
Unfortunately, new guidelines continue to ignore the role of pathogens, virulence, sites of infection and lower-socio-economic settings. Additionally, it remains to be seen whether parasitic, viral and fungal conditions, common in LMIC, should be lumped with bacterial infections in the definition of sepsis. MARS -India will allow the investigators to compare these parameters and those of multi-drug resistant (MDR) pathogens on the impact of the host response and outcomes in sepsis. Not least develop an accurate temporal association of endotypes and detailed understanding of the immune suppressed phenotype. A functional immunology approach throughout and correlations with changes in the gut microbiome will further fortify our understanding of sepsis pathophysiology to help establish a 'sepsis fingerprint' and framework for novel interventions in future. Epidemiology data in itself will considerably heighten our understanding towards a global perspective on sepsis.
Furthermore, little guidance is offered in the Surviving Sepsis Guidelines toward optimal management of the seemingly cured post-acute sepsis patient, who is commonly readmitted with an infection or worse has a significantly reduced life expectancy (>40% 1yr mortality in some studies). MARS-India will also aim to establish the burden of this stage of sepsis in a LMIC setting and study the underpinning pathophysiology in more detail to establish groundwork in uncovering pathways for future therapeutic targeting.
It is apparent that biomarkers reflecting activity of targetable immunological pathways will be of paramount importance in managing the septic patient in future.
- Conditions
- Sepsis, Septic Shock, Sepsis Syndrome
- Keywords
- Pneumonia, Infection, Tropical Infection, Endotypes, Biomarkers, Immunephenotyping, Lower middle-income countries (LMIC), Microbiome, Post-sepsis survival, Multi-omics
- Medical subject headings
- Sepsis, Shock, Septic, Systemic Inflammatory Response Syndrome, Pneumonia, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Septic/septic shock patients | Patients with underlying confirmed or probable cause of infection leading to sepsis or septic shock will form the active group of interest. | |
| Non-septic/sterile inflammation patients | Patient with severe trauma, severe burns and patients admitted to ICU after major surgery or pancreatitis. Active comparator group. | |
| Healthy control patients | Active comparator group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular information of individual host-pathogen response and outcomes in sepsis.
Using RNA sequencing the investigators will map the transcriptional picture of sepsis in a tropical LMIC setting and also map the changes longitudinally.
Measured: 2 years
Gut microbiome alterations in correlation to sepsis endotypes and associated post sepsis mortality/re-admission.
This will make use of 16S PCR and shotgun metagenomic sequencing.
Measured: 3 years
Secondary outcomes (2)
Quantify mortality, morbidity and re-admissions in sepsis survivors from a LMIC setting.
Patients surviving sepsis will be followed up for 6 months post discharge.
Measured: 2.5 years
Stratification of septic patients by severity and type of immune response to infection.
This will utilise a multi-omics approach and up-to-date bioinformatic techniques to bring together the previous outcomes with functional immunology profiles. Ultimate aim will be to generate a novel biomarker panel.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2018
- Study start6 Dec 2018
- Primary completion31 Jul 2020 (estimated)
- Study completion11 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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
- 550 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Kasturba Medical College, BioMérieux
- Responsible party
- Principal investigator, W. J. Wiersinga, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Chiranjay Mukhopadhyay, MD, Phd, Principal investigator, Associate Dean and Professor Department of Microbiology, KMC ManipalWillem Joost Wiersinga, MD, PhD, Principal investigator, Professor of Medicine, Chair Devision of Infectious Diseases and head of infectious diseases research group at the centre for experimental and molecular medicine (CEMM), Amsterdam UMC (AMC)Tom van der Poll, Principal investigator, Professor of Medicine and Chair department of Medicine, Amsterdam UMC (AMC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03727243
- Sponsor's protocol ID
- 371/2018
- Acronym
- MARS-India
- Status last verified
- Jan 2019
- First submitted
- 26 Oct 2018
- Last updated
- 4 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Virk HS, Biemond JJ, Earny VA, Chowdhury S, Frolke RI, Khanna SM, Shanbhag V, Rao S, Acharya RV, Balakrishnan JM, Eshwara VK, Varma MD, van der Poll T, Wiersinga WJ, Mukhopadhyay C. Unraveling Sepsis Epidemiology in a Low- and Middle-Income Intensive Care Setting Reveals the Alarming Burden of Tropical Infections and Antimicrobial Resistance: A Prospective Observational Study (MARS-India). Clin Infect Dis. 2025 Feb 5;80(1):101-107. doi: 10.1093/cid/ciae486.
PubMed 39352692
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Diagnosis and Risk Stratification of Sepsis in India
- ClinicalTrials.gov ID
- NCT03727243
- Acronym / sponsor ID
- MARS-India / 371/2018
- Conditions
- Sepsis, Septic Shock, Sepsis Syndrome
- Keywords
- Pneumonia, Infection, Tropical Infection, Endotypes, Biomarkers, Immunephenotyping, Lower middle-income countries (LMIC), Microbiome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 550 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Kasturba Medical College, BioMérieux
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- 31 Jul 2020 (estimated)
- Study completion
- 11 Jun 2021 (estimated)
- First posted
- 1 Nov 2018 (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.
Background: Globally, sepsis is common with an estimated population incidence of 437 cases per 100, 000 person-years and acute mortality of 26%, one of the few major medical conditions whose incidence and resulting mortality continues to rise. However, true burden is likely significantly higher as a recent meta- analysis could find no data from LMIC where 87% of the world's population resides.
Objective: Generate new knowledge that will eventually provide rapid and accurate information about an individual patient suffering from sepsis (or critical illness), including which type of microorganism is responsible for the infection and the severity and stage of the patient's immune response.
Methods: MARS-India will be a prospective longitudinal, single-centre observational study, conducted in mixed ICU's of a >2000 bedded tertiary teaching hospital in Manipal, India. The investigators will recruit to three groups- sex and age-matched healthy volunteers (n=150) and patients diagnosed with sepsis/septic shock or non-infectious ICU admissions such as severe trauma, severe burns and patients admitted to ICU after major surgery (n=400). The investigators have optimised a workflow to follow and describe the immunoinflammatory status of septic patients (as well as severe trauma/burn and major surgery) during the first 6 months after their initial injury. At fixed time points the investigators will collect blood in PaxGene, heparin, citrate and EDTA tubes in addition to routine bloods and microbiological samples. Rectal swabs and stool will also be taken for microbiome analysis. Immune functional tests will be performed to determine whole-blood cytokine/chemokine production in response to ex-vivo stimulation using an 8-panel assay. Additionally, complete immunophenotyping using flow cytometry including HLA-DR expression and lymphocyte subsets will be obtained.
Detailed description
New sepsis 3.0 definition has for the first time included a dysregulated host response to infection as the cause of organ dysfunction, however, sepsis remains a highly heterogeneous syndrome without an accepted definition of what constitutes a dysregulated host response. The field is only now realising that inclusion of specific characteristics of the host response (transcriptomic or immunological profiles) facilitate stratification of patients with sepsis into subgroups (endotypes), allowing for prognostic enrichment and targeted therapeutic intervention.
Unfortunately, new guidelines continue to ignore the role of pathogens, virulence, sites of infection and lower-socio-economic settings. Additionally, it remains to be seen whether parasitic, viral and fungal conditions, common in LMIC, should be lumped with bacterial infections in the definition of sepsis. MARS -India will allow the investigators to compare these parameters and those of multi-drug resistant (MDR) pathogens on the impact of the host response and outcomes in sepsis. Not least develop an accurate temporal association of endotypes and detailed understanding of the immune suppressed phenotype. A functional immunology approach throughout and correlations with changes in the gut microbiome will further fortify our understanding of sepsis pathophysiology to help establish a 'sepsis fingerprint' and framework for novel interventions in future. Epidemiology data in itself will considerably heighten our understanding towards a global perspective on sepsis.
Furthermore, little guidance is offered in the Surviving Sepsis Guidelines toward optimal management of the seemingly cured post-acute sepsis patient, who is commonly readmitted with an infection or worse has a significantly reduced life expectancy (>40% 1yr mortality in some studies). MARS-India will also aim to establish the burden of this stage of sepsis in a LMIC setting and study the underpinning pathophysiology in more detail to establish groundwork in uncovering pathways for future therapeutic targeting.
It is apparent that biomarkers reflecting activity of targetable immunological pathways will be of paramount importance in managing the septic patient in future.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Septic/septic shock patients | – | –Patients with underlying confirmed or probable cause of infection leading to sepsis or septic shock will form the active group of interest. |
| Non-septic/sterile inflammation patients | – | –Patient with severe trauma, severe burns and patients admitted to ICU after major surgery or pancreatitis. Active comparator group. |
| Healthy control patients | – | –Active comparator group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients hospitalised in the general, emergency and neuro ICU's of Kasturba Hospital, Manipal. KMC hospital is a >2000 bedded tertiary care hospital that treats patients from a wide geographic area which can sometimes stretch beyond the state of Karnataka itself. Most patients will be from a mixture of urban and rural settings, with tropical infectious presentations varying throughout the year.
Key inclusion criteria (5 listed)
- All patients aged 18 years and over in the intensive care units of Kasturba Hospital, Manipal (and meeting the study population definitions below)
- Sepsis - defined as the presence of infection diagnosed within 24 hours of ICU admission with probable or definite likelihood, accompanied by organ dysfunction represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. Septic shock is defined as per the recent Sepsis 3.0 consensus guidelines.
- Serious trauma within 24 hours, with patient directly admitted to ICU (injury severity score (ISS) >15).
- Severe burns (total surface area burned >30%).
- Major surgery or pancreatitis/non-infectious inflammation.
Key exclusion criteria (9 listed)
- Pregnant or breast-feeding women
- Patients with a 'withdrawal of care' decision at time of inclusion
- Patients whose anticipated duration of hospitalisation in ICU is estimated <48 hours
- Extra-corporeal circulation in the month preceding inclusion in the case of cardiac surgery
- Patient with restricted liberty or under legal protection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Molecular information of individual host-pathogen response and outcomes in sepsis.
Time frame: 2 years
Using RNA sequencing the investigators will map the transcriptional picture of sepsis in a tropical LMIC setting and also map the changes longitudinally.
Gut microbiome alterations in correlation to sepsis endotypes and associated post sepsis mortality/re-admission.
Time frame: 3 years
This will make use of 16S PCR and shotgun metagenomic sequencing.
2 secondary outcomes
Quantify mortality, morbidity and re-admissions in sepsis survivors from a LMIC setting.
Time frame: 2.5 years
Stratification of septic patients by severity and type of immune response to infection.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
- Derived from this study: PubMed 39352692Virk HS, Biemond JJ, Earny VA, Chowdhury S, Frolke RI, Khanna SM, Shanbhag V, Rao S, Acharya RV, Balakrishnan JM, Eshwara VK, Varma MD, van der Poll T, Wiersinga WJ, Mukhopadhyay C. Unraveling Sepsis Epidemiology in a Low- and Middle-Income Intensive Care Setting Reveals the Alarming Burden of Tropical Infections and Antimicrobial Resistance: A Prospective Observational Study (MARS-India). Clin Infect Dis. 2025 Feb 5;80(1):101-107. doi: 10.1093/cid/ciae486.
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
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.
Chiranjay Mukhopadhyay, MD, Phd principal investigator
Associate Dean and Professor Department of Microbiology, KMC Manipal
Willem Joost Wiersinga, MD, PhD principal investigator
Professor of Medicine, Chair Devision of Infectious Diseases and head of infectious diseases research group at the centre for experimental and molecular medicine (CEMM), Amsterdam UMC (AMC)
Tom van der Poll principal investigator
Professor of Medicine and Chair department of Medicine, Amsterdam UMC (AMC)
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 Septic Shock, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in India.
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 5 inclusion and 9 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 4 Jan 2019. 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 India. 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?
Contact Harjeet Singh Virk, MD (+31205665910, h.s.virk@amc.uva.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Molecular information of individual host-pathogen response and outcomes in sepsis. (time frame: 2 years). 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?
On the ClinicalTrials.gov record for NCT03727243, which also lists 1 linked publication.
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 4 Jan 2019.