Sepsis Characterization in Kilimanjaro

Study Overview
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Brief Summary
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The aim of this study is to prospectively evaluate the barriers to care, evaluation, clinical practices, and outcomes for patients presenting with sepsis to hospitals in the Kilimanjaro Region of northern Tanzania. This will include an assessment of timing and selection of antimicrobials and administration and volume of intravenous fluids. The study also aims to characterize sepsis sub-types in the epidemiologic context of northern Tanzania using statistical clustering techniques of clinical variables and of host immune response patterns.

Detailed Description
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A prospective observational cohort study of adolescent and adult patients with sepsis presenting to hospitals in the Kilimanjaro Region, Tanzania. Participants ≥10 years of age with suspected infection and the presence of two of the following will be enrolled: (1) tympanic temperature > 38°C or < 36°C, (2) heart rate > 90 beats/minute, (3) respiratory rate > 20 breaths/minute. Participants will be observed in the Emergency Department and during admission. The following data will be collected: demographics and medical history; history of present illness; laboratory and microbiological workup; antimicrobial selection and timing; intravenous fluid timing and volume. Vital status will be determined at 7 days, hospital discharge, and 28 days post-presentation. An enrollment of up to 1250 patients with sepsis is expected over a two-year period. This study is expected to produce additional descriptive data of sepsis epidemiology and current practice in sSA. The data will yield important insights regarding key care practices for sepsis, including antimicrobial and intravenous fluid management. Outcomes of patients with sepsis will be described, including an assessment for correlations between current care practices and mortality. Characterization of potential sepsis sub-types will be undertaken in two domains: 1) clinical characterization via a robust battery of routine clinical laboratories (chemistry, hematology, coagulation studies), vital signs, routine clinical signs and anthropometry; 2) host immune response characterization by analysis of mRNA transcriptome expression in RNA-stabilized whole blood samples. The goal of the sub-type characterization is to identity discrete and clinically relevant sepsis phenotypes, and in doing so eventually help optimize evaluation and management of sepsis specific to the populations and health systems in sub-Saharan Africa. Detailed etiologic investigations will also take place, including blood culture, blood parasite smears, and viral respiratory testing of nasopharyngeal samples; for patients living with HIV, additional evaluations will include serum cryptococcal antigen, urine lipoarabinomannan assay (TB-LAM) and MycoFLytic blood culture. Collectively, the data collected in this observational cohort study will contribute to further developing sepsis management bundles better suited to settings sub-Saharan Africa.

Official Title
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Sepsis in Sub-Saharan Africa: a Prospective Observational Study of Clinical Characteristics, Management, Outcomes, and Barriers to Care in Northern Tanzania

Conditions
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Sepsis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persons ≥ 10 years of age presenting to hospital suspected to have an infection and meeting two of the following vital signs criteria: tympanic >38°C or < 36°C a heart rate > 90 beats per minute a respiratory rate of > 20 breaths per minute Exclusion Criteria: patient with a language barrier pregnant female a refugee a prisoner

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with sepsis<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sepsis sub-types derived from clinical characteristics. | Number of sepsis subtypes identified by statistical clustering analysis of clinical characteristics. | Up to 4 years | 
| Sepsis sub-types derived from host immune response to infection. | Number of sepsis subtypes identified by statistical clustering analysis of patient immune response as measured by mRNA gene expression transcrimptomic signature. | Up to 4 years | 
| Mortality due to sepsis | Time (measured in hours) to fatal event among patients with sepsis as measured by study staff observation or interview. | Within 28 days of presentation to hospital triage | 
| 28-day mortality due to sepsis | Percentage of sepsis patients alive at 28 days after presentation to hospital triage as measured by study staff observation or interview. | Within 28 days of presentation to hospital triage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay in care-seeking for sepsis | Percent of sepsis patients with a World Health Organization severity sign who delayed seeking medical care outside the home > 24 hours after onset of the severity sign as measured by patient/patient representative report. | Within 24 hours of presentation to hospital triage | 
| Factors that slowed care-seeking | Number of factors that slowed down the decision to seek care at hospital for present illness as measured by patient/patient representative report. | Within 24 hours of presentation to hospital triage | 
| Time to antibiotics among patients with sepsis | Time in hours from initial presentation at hospital triage to administration of antibiotics among patients with sepsis as measured by study staff observation and hospital records. | Within 24 hours of presentation to hospital triage | 
| Intravenous venous fluid resuscitation among patients with sepsis | Percentage of sepsis patients who receive intravenous fluids within 6 hours of presentation at hospital triage as measured by study staff observation and real-time review of hospital charting records. | Within 24 hours of presentation to hospital triage | 
| Volume of intravenous fluid resuscitation among patients with sepsis | Volume (measured in liters) of intravenous fluids received within 6 hours presentation at hospital triage as measured by study staff observation and real-time review of hospital charting records. | Within 6 hours of presentation to hospital triage | 
| In-hospital mortality due to sepsis | Percentage of sepsis patients who survive to hospital discharge as measured by study staff observation. | Within 28 days of presentation to hospital triage | 
| 7-day mortality due to sepsis | Percentage of sepsis patients alive at 7 days after presentation to hospital triage as measured by study staff observation or interview. | Within 7 days of presentation to hospital triage | 
| Clinical characteristic sub-type non-classification | Percentage of sepsis patients who could not be classified into a sepsis sub-type derived by statistical clustering of clinical characteristics. | Up to 4 years | 
| Immune response sub-types non-classification | Percentage of sepsis patients who could not be classified into a sepsis sub-type derived by statistical clustering of patient immune response as measured by mRNA gene expression transcrimptomic signature. | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Africa, Tanzania