Sepsis, Severe Sepsis, Tuberculosis
Conditions
Keywords
Sepsis, Severe sepsis, Tuberculosis, Bundle, Zambia
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.
Interventions
This protocol consists of an early aggressive fluid strategy, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.
OTHERUsual care
Patients are managed according to admitting doctors' orders
Sponsors
National Institutes of Health (NIH)
Fogarty International Center of the National Institute of Health
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In-hospital all cause mortality | During hospitalization, expected average 14 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
| 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. |
| 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. |
Countries
Zambia
Outcome results
None listed