Simplified Severe Sepsis Protocol-2 (SSSP-2) in Zambia (SSSP-2)

Simplified Severe Sepsis Protocol-2 (SSSP-2): A Randomized Controlled Trial of a Bundled Intervention for Severe Sepsis at the University Teaching Hospital in Zambia

This study is a randomized control trial assessing the impact of a simple evidence-based protocol for the treatment severe sepsis with hypotension in Zambia. This is a follow-up study to the Simplified Severe Sepsis Protocol (SSSP) study. 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 and hypotension.

Study Overview

• Status: Completed
• Conditions: Sepsis; Tuberculosis; Severe Sepsis
• Intervention / Treatment: Other: Usual care; 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. In sub-Saharan Africa, simple therapies such as IV fluids and early antibiotics are frequently under-utilized. Studies of fluid interventions in the region, however, have demonstrated conflicting results. Outcomes in septic patients may be further affected by delays in the diagnosis of tuberculosis-associated severe sepsis.

The aims of this study are (1) To assess the impact on survival of a simple evidence-based protocol for severe sepsis with hypotensionor septic shock, (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, and (4) To assess the performance of the Xpert TB/RIF rapid PCR system and urine lipoarabinomannan assay for diagnosing tuberculosis in HIV positive patients with severe sepsis.

• Study Type: Interventional
• Enrollment (Actual): 212
• 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:

• infection suspected by the treating physician
• 2 or more of the following 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 of the following:
• Systolic blood pressure (SBP) ≤ 90 mm Hg
• Mean arterial blood pressure (MAP) ≤ 65 mm Hg

Exclusion Criteria:

• Gastrointestinal bleed in the absence of fever
• Need for immediate surgery
• Respiratory rate greater than 40/min with oxygen saturation less than 90%
• Suspected congestive heart failure exacerbation
• End-stage renal disease
• Raised jugular venous pressure (JVP) at baseline
• Currently incarcerated

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
Active Comparator: Usual care; Patients are managed according to admitting doctors' orders. Blood cultures are drawn in all patients. Antibiotics are specified by the admitting doctors.	Other: Usual care; Patients are managed according to admitting doctors' orders
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. Antibiotics are specified by the admitting doctors.	Other: Simplified severe sepsis protocol; This protocol consists of an early aggressive fluid strategy, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.

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

Publications and helpful links

General Publications

• Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Mabula C, Bwalya M, Bernard GR. Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial. JAMA. 2017 Oct 3;318(13):1233-1240. doi: 10.1001/jama.2017.10913.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimate): August 13, 2012

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: Tuberculosis; Sepsis; Zambia; Severe sepsis; Bundle
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Sepsis; Toxemia; Tuberculosis
• Other Study ID Numbers: SSSP-2; R24TW007988 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Requests for data sharing should be directed to PI. PI will then confer with Zambian co-PI to confirm that data sharing is allowable by Zambian law.