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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Sepsis, Severe Sepsis, Tuberculosis

Intervention / Treatment
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* Other: Simplified severe sepsis protocol
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual care<br>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<br>* Patients are managed according to admitting doctors' orders<br>|
| Experimental: Simplified Severe Sepsis Protocol<br>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<br>* This protocol consists of an early aggressive fluid strategy, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Severe sepsis, Tuberculosis, Bundle, Zambia