Simplified Severe Sepsis Protocol 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 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.

Detailed Description
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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.

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

Conditions
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Sepsis, Severe Sepsis

Intervention / Treatment
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* Other: Simplified Severe Sepsis Protocol


Participation Criteria
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Eligibility Criteria
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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

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 |
| --- | --- |
| 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. | Other: Simplified Severe Sepsis Protocol<br>* Early fluid protocol, early blood cultures and antibiotics; blood cultures and titrated dopamine in selected patients; monitoring based on vital signs and physical examination<br>|
| Active Comparator: Usual care<br>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<br>* Early fluid protocol, early blood cultures and antibiotics; blood cultures and titrated dopamine in selected patients; monitoring based on vital signs and physical examination<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, Protocol, Zambia