Sepsis Characterization in Kilimanjaro

Completed

• Conditions: Sepsis

• Registration Number: NCT05139459
• Lead Sponsor: Duke University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-11-11
• Study First Submitted QC: 2021-11-30
• Study First Posted: 2021-12-01
• Study Start: 2022-01-17
• Primary Completion: 2023-11-03
• Study Completion: 2023-11-03
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 499

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Factors that slowed care-seeking	Within 24 hours of presentation to hospital triage	Number of factors that slowed down the decision to seek care at hospital for present illness as measured by patient/patient representative report.
Delay in care-seeking for sepsis	Within 24 hours of presentation to hospital triage	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.
Time to antibiotics among patients with sepsis	Within 24 hours of presentation to hospital triage	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.
Intravenous venous fluid resuscitation among patients with sepsis	Within 24 hours of presentation to hospital triage	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.
Clinical characteristic sub-type non-classification	Up to 4 years	Percentage of sepsis patients who could not be classified into a sepsis sub-type derived by statistical clustering of clinical characteristics.
In-hospital mortality due to sepsis	Within 28 days of presentation to hospital triage	Percentage of sepsis patients who survive to hospital discharge as measured by study staff observation.
7-day mortality due to sepsis	Within 7 days of presentation to hospital triage	Percentage of sepsis patients alive at 7 days after presentation to hospital triage as measured by study staff observation or interview.
Immune response sub-types non-classification	Up to 4 years	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.
Volume of intravenous fluid resuscitation among patients with sepsis	Within 6 hours of presentation to hospital triage	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.

Trial Locations

Locations (1)

Duke University Medical Centre; 🇺🇸 Durham, North Carolina, United States