Molecular Diagnosis and Risk Stratification of Sepsis in India

NCT03727243 | Unknown

• 1 other identifier: 371/2018
• Study Type: observational
• Target: 550
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  3 years

Secondary Outcomes (2)

• Quantify mortality, morbidity and re-admissions in sepsis survivors from a LMIC setting.

  2.5 years

• Stratification of septic patients by severity and type of immune response to infection.

  3 years

Study Arms (3)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• Pregnant or breast-feeding women
• Patients whose anticipated duration of hospitalisation in ICU is estimated \<48 hours
• 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)

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Kasturba Medical College: collaborator
• BioMérieux: collaborator

Study Sites (1)

Kasturba Hospital, Kasturba Medical College (KMC), Manipal Academy of Higher Education (MAHE)

Udupi, Karnataka, 576104, India

RECRUITING

Related Publications (1)

• 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.

  PMID: 39352692 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, RNA, DNA, PBMCs, Faeces

MeSH Terms

Conditions

Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Pneumonia; Infections

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harjeet Singh Virk, MD

CONTACT

+31205665910; h.s.virk@amc.uva.nl

Willem Joost Wiersinga, MD, PhD

CONTACT

+31205665910; w.j.wiersinga@amc.uva.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Chair division of Infectious Diseases and head of infectious diseases research group at the centre for experimental and molecular medicine (CEMM)

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: November 1, 2018
• Study Start: December 6, 2018
• Primary Completion: July 31, 2020
• Study Completion: June 11, 2021
• Last Updated: January 4, 2019

Record last verified: 2019-01

Locations

IN (1)