Simplified Severe Sepsis Protocol in Zambia (SSSP)

Improving Sepsis Diagnosis and Treatment: Simplified Severe Sepsis Protocol (SSSP)

This study is a randomized control trial assessing the impact of a simple evidence-based protocol for the treatment severe sepsis in Zambia. The intervention protocol consists of a scheduled fluid regimen, early blood culture and antibiotics, and dopamine and blood transfusion when necessary. It is hypothesized that the protocol will significantly decrease in-hospital mortality in patients with severe sepsis.

Study Overview

• Status: Terminated
• Conditions: Sepsis; Severe Sepsis
• Intervention / Treatment: Other: Simplified Severe Sepsis Protocol

Detailed Description

In recent years, evidence-based protocols of bundled therapies have improved survival of severe sepsis in developed countries. However, in sub-Saharan Africa, simple therapies such as IV fluids and early antibiotics are frequently under-utilized. Furthermore, although tuberculosis is a common cause of severe sepsis in the region, accurate and timely diagnosis of tuberculosis-associated severe sepsis remains elusive.

The aims of this study are (1) To assess the impact on survival of a simple evidence-based protocol for severe sepsis, (2) To evaluate the cost of implementation for a simplified severe sepsis protocol (3) To develop a clinical diagnostic score for identifying tuberculosis in HIV positive patients with severe sepsis (4) To assess the performance of the Xpert TB/RIF rapid PCR system for diagnosing tuberculosis in HIV positive patients with severe sepsis.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Zambia
  • Lusaka, Zambia
    • University Teaching 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:

• Age 18 or older
• Suspected infection

• 2 or more of SIRS criteria:

  • Heart rate >90/min
  • Respiratory rate >20/min
  • Temperature >= 38° C or <= 36° C
  • White blood count > 12,000 or < 4,000/µL

• 1 or more of the following signs of end-organ dysfunction

  • Systolic blood pressure < 90 mm Hg
  • Mean arterial blood pressure (MAP) < 65 mm Hg
  • Confusion/altered mentation
  • Urine output < 0.5 mL/kg/hr
  • Creatinine increase > 0.5 mg/dL
  • Creatinine > 0.5 mg/dL above upper limit of normal
  • Platelet < 100x109/L
  • Respiratory rate > 40/min
  • Jaundice

Exclusion Criteria:

• GI bleed
• Need for urgent surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simplified Severe Sepsis Protocol; This protocol consists of an early aggressive fluid strategy, early blood cultures and antibiotics, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.	Other: Simplified Severe Sepsis Protocol; Early fluid protocol, early blood cultures and antibiotics; blood cultures and titrated dopamine in selected patients; monitoring based on vital signs and physical examination
Active Comparator: Usual care; Early blood cultures and antibiotics. Monitoring by study nurses as in experimental arm. Other interventions are according to admitting (non-study) doctors' orders.	Other: Simplified Severe Sepsis Protocol; Early fluid protocol, early blood cultures and antibiotics; blood cultures and titrated dopamine in selected patients; monitoring based on vital signs and physical examination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In-hospital all cause mortality	During hospitalization, expected average 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day all-cause mortality		28-day
In-hospital all cause mortality adjusted for illness severity	Adjusted for SAPS3 score	During hospitalization, expected average 14 days
28-day all cause mortality adjusted for baseline illness severity	Adjusted for SAPS3 score	28-day
Cumulative adverse events	A composite outcome consisting of dopamine extravasation, dopamine-associated tissue ischemia or necrosis, iatrogenic pulmonary oedema, and transfusion-related adverse events.	During hospitalization, expected average 14 days
Treatment cost per patient	A budget impact analysis will determine the cost of treatment per patient using a mix of direct measurements and micro-cost observation.	During hospitalization, expected average 14 days
Antibiotic changed due to culture results	The proportion of patients whose antibiotic regimen was changed due to information obtained from blood culture results.	During hospitalization, expected average 14 days

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Collaborators: National Institutes of Health (NIH); Fogarty International Center of the National Institute of Health
• Investigators: Principal Investigator: Benjamin L Andrews, MD, Vanderbilt University and University of Zambia

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: October 5, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (Estimate): October 10, 2011

Study Record Updates

• Last Update Posted (Actual): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Sepsis; Severe Sepsis; Zambia; Protocol
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: SSSP; R24TW007988 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No