Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03727243
Other study ID # 371/2018
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date December 6, 2018
Est. completion date June 11, 2021

Study information

Verified date January 2019
Source Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Contact Harjeet Singh Virk, MD
Phone +31205665910
Email h.s.virk@amc.uva.nl
Is FDA regulated No
Health authority
Study type Observational

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 550
Est. completion date June 11, 2021
Est. primary completion date July 31, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility 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)

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
India Kasturba Hospital, Kasturba Medical College (KMC), Manipal Academy of Higher Education (MAHE) Udupi Karnataka

Sponsors (3)

Lead Sponsor Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) BioMérieux, Kasturba Medical College

Country where clinical trial is conducted

India, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 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. 2.5 years
Secondary 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. 3 years
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05095324 - The Biomarker Prediction Model of Septic Risk in Infected Patients
Completed NCT02714595 - Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens Phase 3
Completed NCT03644030 - Phase Angle, Lean Body Mass Index and Tissue Edema and Immediate Outcome of Cardiac Surgery Patients
Completed NCT02867267 - The Efficacy and Safety of Ta1 for Sepsis Phase 3
Completed NCT04804306 - Sepsis Post Market Clinical Utility Simple Endpoint Study - HUMC
Recruiting NCT05578196 - Fecal Microbial Transplantation in Critically Ill Patients With Severe Infections. N/A
Terminated NCT04117568 - The Role of Emergency Neutrophils and Glycans in Postoperative and Septic Patients
Completed NCT03550794 - Thiamine as a Renal Protective Agent in Septic Shock Phase 2
Completed NCT04332861 - Evaluation of Infection in Obstructing Urolithiasis
Completed NCT04227652 - Control of Fever in Septic Patients N/A
Enrolling by invitation NCT05052203 - Researching the Effects of Sepsis on Quality Of Life, Vitality, Epigenome and Gene Expression During RecoverY From Sepsis
Terminated NCT03335124 - The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock Phase 4
Recruiting NCT04005001 - Machine Learning Sepsis Alert Notification Using Clinical Data Phase 2
Completed NCT03258684 - Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Sepsis and Septic Shock N/A
Recruiting NCT05217836 - Iron Metabolism Disorders in Patients With Sepsis or Septic Shock.
Completed NCT05018546 - Safety and Efficacy of Different Irrigation System in Retrograde Intrarenal Surgery N/A
Completed NCT03295825 - Heparin Binding Protein in Early Sepsis Diagnosis N/A
Not yet recruiting NCT06045130 - PUFAs in Preterm Infants
Not yet recruiting NCT05361135 - 18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in S. Aureus Bacteraemia N/A
Not yet recruiting NCT05443854 - Impact of Aminoglycosides-based Antibiotics Combination and Protective Isolation on Outcomes in Critically-ill Neutropenic Patients With Sepsis: (Combination-Lock01) Phase 3