Epidemiology, Acute Management, and Outcomes of Patients With Sepsis Presenting to a Referral Hospital in Western Kenya

Sepsis is a clinical syndrome representing deranged hemodynamics (such as tachycardia) secondary to severe infection. In high-income countries (HICs), early resuscitation of septic patients with protocol-driven therapy, including quantitative fluid administration guided by invasive monitoring, has resulted in improved outcomes for septic patients. Prevalence and mortality of sepsis are thought to be higher in sub-Saharan Africa (SSA) than in high-income countries; however, most hospitals in SSA lack the technology and resources necessary to implement the resuscitation protocols used in HICs and therefore, mortality from sepsis remains high. The World Health Organization (WHO) has recently disseminated an algorithm for resuscitation of septic patients in low resource settings. This algorithm is based on expert consensus only, and its efficacy has never been tested.

This study will be conducted in the Casualty Department of Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya.

The purpose of this study is to describe the epidemiology of patients presenting with severe sepsis, to examine the microbiology causing severe sepsis, to describe current management and outcomes for severe sepsis, and to test the effect of implementation of the WHO resuscitation algorithm at MTRH.

The study design is a prospective before and after clinical trial. In an initial observational phase, adult patients presenting to the MTRH Casualty Department with sepsis and severe sepsis (the latter of which will be defined by elevated lactate) will be enrolled into a prospective observational cohort. Demographic data, medical characteristics, and microbiological studies will be obtained, then the management and outcomes of these patients will be observed. In a second phase, patients with sepsis will continue to be enrolled into a prospective observational cohort, while patients with severe sepsis will be enrolled into an intervention group. Patients in the intervention group will be managed according to the WHO resuscitation algorithm. Specifically, the WHO algorithm involves fluid boluses guided by vital signs and physical exam findings, rapid and early administration of empiric antibiotics, and frequent patient monitoring. The outcomes of interest are achievement of lactate clearance, which is a correlate of tissue perfusion, as well as 24-hour, in-hospital, and 30-day mortality.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Severe Sepsis
• Intervention / Treatment: Other: WHO algorithm of fluid boluses guided by physical examination; Other: Frequent patient monitoring; Other: Early administration of empiric antibiotics; Other: Oxygen delivery; Other: Correction of hypoglycemia; Other: Correction of severe anemia

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Eldoret, Kenya
    • Moi Teaching and Referral Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Presenting to MTRH Casualty Department for acute medical care
• Suspected infection, in the judgment of the managing clinician
• At least 2 of the following: axillary temperature >37.5°C or <35.5°C or core temperature >38.0°C or <36.0°C; heart rate >90 beats per minute; respiratory rate >20 breaths per minute; or systolic blood pressure <100 mmHg

Exclusion Criteria:

• Lack of basic language skills in either English or Kiswahili
• Pregnancy
• Congestive heart failure or valvular heart disease (as a known prior diagnosis or in the judgment of the managing clinician)
• Need for immediate surgery (within 6 hours) in the judgment of the managing clinician
• Inability to consent to study participation and lack of accompaniment by a family member or other surrogate who can provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WHO intervention; This arm will be treated with the 2011 WHO sepsis recommendations for the first 6 hours of their hospitalization. The WHO recommendations involve fluid boluses guided by vital signs and physical exam, frequent patient monitoring, rapid and early administration of empiric antibiotics, oxygen delivery, correction of hypoglycemia, and correction of severe anemia.	Other: WHO algorithm of fluid boluses guided by physical examination; Other: Frequent patient monitoring; Vital signs and physical exam every 30-60 minutes; Other: Early administration of empiric antibiotics; Clinician will be prompted to administer antibiotics within 60 minutes; Other: Oxygen delivery; Other: Correction of hypoglycemia; If blood glucose is less than 3.0 mmol/L, IV dextrose will be administered; Other: Correction of severe anemia; If hemoglobin is less than 7 mg/dL, clinician will be prompted to offer blood transfusion
No Intervention: Standard care; This arm will be managed per standard care by the hospital clinicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate clearance (difference in lactate [mmol/L] at study enrollment and 6 hours after study enrollment) as a measure of efficacy	Lactate level will be measured at study enrollment (time 0) and 6 hours after study enrollment (time 6). Lactate clearance will be reported as the difference between time 0 and time 6 lactate, as a fraction of time 0 lactate.	enrollment, 6 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	24 hours, in-hospital, and 30 days
Number of subjects with adverse effects as a measure of safety	6 hours, 24 hours, in-hospital, and 30 days

Other Outcome Measures

Outcome Measure	Time Frame
Time of first antibiotic delivery	1 hour
IV fluid volume (ml)	6 hours, 24 hours, in-hospital

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Fogarty International Center of the National Institute of Health; Moi University
• Investigators: Principal Investigator: Nathan M Thielman, MD, MPH, Duke University; Principal Investigator: Charles Kwobah, MBChB, MMed, Moi University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 27, 2015

Study Record Updates

• Last Update Posted (Actual): January 5, 2018
• Last Update Submitted That Met QC Criteria: January 4, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: Pro00056846; R25TW009337 (U.S. NIH Grant/Contract)