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

Not Applicable

Completed

• Conditions: Tuberculosis; Sepsis; Severe Sepsis
• Interventions: Other: Usual care; Other: Simplified severe sepsis protocol

• Registration Number: NCT01663701
• Lead Sponsor: Vanderbilt University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-08-08
• Study First Submitted QC: 2012-08-10
• Study First Posted: 2012-08-13
• Study Start: 2012-10
• Primary Completion: 2013-11
• Study Completion: 2014-01
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-23
• Last Update Posted: 2021-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 212

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Usual care	Usual care	Patients are managed according to admitting doctors' orders. Blood cultures are drawn in all patients. Antibiotics are specified by the admitting doctors.
Simplified Severe Sepsis Protocol	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.

Primary Outcome Measures

Name	Time	Method
In-hospital all cause mortality	During hospitalization, expected average 14 days

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Teaching Hospital; 🇿🇲 Lusaka, Zambia