Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Molecular Diagnosis and Risk Stratification of Sepsis in India (MARS-India)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03727243
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : January 4, 2019
Sponsor:
Collaborators:
Kasturba Medical College
BioMérieux
Information provided by (Responsible Party):
W. J. Wiersinga, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Tracking Information
First Submitted Date October 26, 2018
First Posted Date November 1, 2018
Last Update Posted Date January 4, 2019
Actual Study Start Date December 6, 2018
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 30, 2018)
  • 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.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03727243 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: October 30, 2018)
  • Quantify mortality, morbidity and re-admissions in sepsis survivors from a LMIC setting. [ Time Frame: 2.5 years ]
    Patients surviving sepsis will be followed up for 6 months post discharge.
  • Stratification of septic patients by severity and type of immune response to infection. [ Time Frame: 3 years ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Molecular Diagnosis and Risk Stratification of Sepsis in India
Official Title Molecular Diagnosis and Risk Stratification of Sepsis in India
Brief 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. 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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Whole blood, plasma, RNA, DNA, PBMCs, Faeces
Sampling Method Probability Sample
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.
Condition
  • Sepsis
  • Septic Shock
  • Sepsis Syndrome
Intervention Not Provided
Study Groups/Cohorts
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 30, 2018)
550
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 11, 2021
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Harjeet Singh Virk, MD +31205665910 h.s.virk@amc.uva.nl
Contact: Willem Joost Wiersinga, MD, PhD +31205665910 w.j.wiersinga@amc.uva.nl
Listed Location Countries India
Removed Location Countries  
 
Administrative Information
NCT Number NCT03727243
Other Study ID Numbers 371/2018
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party W. J. Wiersinga, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Sponsor Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
  • Kasturba Medical College
  • BioMérieux
Investigators
Principal Investigator: Chiranjay Mukhopadhyay, MD, Phd Associate Dean and Professor Department of Microbiology, KMC Manipal
Principal Investigator: Willem Joost Wiersinga, MD, PhD 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)
Principal Investigator: Tom van der Poll Professor of Medicine and Chair department of Medicine, Amsterdam UMC (AMC)
PRS Account Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Verification Date January 2019