Clinical trial NCT05139459: Sepsis Characterization in Kilimanjaro
Official title: Sepsis in Sub-Saharan Africa: a Prospective Observational Study of Clinical Characteristics, Management, Outcomes, and Barriers to Care in Northern Tanzania
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Keywords: Africa
Tanzania
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Kilimanjaro Christian Medical Centre, Tanzania
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2021-12-01
Enrollment: 499
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adolescent and adult patients with sepsis presenting to emergency department or outpatient department at hospitals in Kilimanjaro Region, northern Tanzania.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sepsis sub-types derived from clinical characteristics.
timeFrame: Up to 4 years
measure: Sepsis sub-types derived from host immune response to infection.
timeFrame: Up to 4 years
measure: Mortality due to sepsis
timeFrame: Within 28 days of presentation to hospital triage
measure: 28-day mortality due to sepsis
timeFrame: Within 28 days of presentation to hospital triage
Secondary outcomes:
measure: Delay in care-seeking for sepsis
timeFrame: Within 24 hours of presentation to hospital triage
measure: Factors that slowed care-seeking
timeFrame: Within 24 hours of presentation to hospital triage
measure: Time to antibiotics among patients with sepsis
timeFrame: Within 24 hours of presentation to hospital triage
measure: Intravenous venous fluid resuscitation among patients with sepsis
timeFrame: Within 24 hours of presentation to hospital triage
measure: Volume of intravenous fluid resuscitation among patients with sepsis
timeFrame: Within 6 hours of presentation to hospital triage
measure: In-hospital mortality due to sepsis
timeFrame: Within 28 days of presentation to hospital triage
measure: 7-day mortality due to sepsis
timeFrame: Within 7 days of presentation to hospital triage
measure: Clinical characteristic sub-type non-classification
timeFrame: Up to 4 years
measure: Immune response sub-types non-classification
timeFrame: Up to 4 years
Other outcomes:
measure: Sepsis due to respiratory syndrome
timeFrame: Within 24 hours of presentation to hospital triage
measure: Sepsis due to neurologic syndrome
timeFrame: Within 24 hours of presentation to hospital triage
measure: Sepsis due to genito-urinary syndrome
timeFrame: Within 24 hours of presentation to hospital triage
measure: Sepsis due to skin/soft tissue syndrome.
timeFrame: Within 24 hours of presentation to hospital triage
measure: Sepsis due to gastrointestinal syndrome.
timeFrame: Within 24 hours of presentation to hospital triage
measure: Sepsis due to undifferentiated syndrome.
timeFrame: Within 24 hours of presentation to hospital triage
measure: HIV-infection among sepsis patients
timeFrame: Within 24 hours of presentation to hospital triage
measure: Sepsis severity of illness
timeFrame: Within 24 hours of presentation to hospital triage
measure: Pre-specified sub-group analysis: enrolled participants with Sequential Organ Failure Assessment (SOFA) score of 2 or greater.
timeFrame: Up to 4 years
measure: Pre-specified sub-group analysis: enrolled participants with C-reactive protein measurement of 15 mg/L or higher
timeFrame: Up to 4 years
Locations:
city: Durham
country: United States
facility: Duke University Medical Centre
state: North Carolina
Study officials:
affiliation: Duke University
name: Matthew P Rubach, MD
role: PRINCIPAL_INVESTIGATOR
References: