Clinical trial NCT01663701: Simplified Severe Sepsis Protocol-2 (SSSP-2) in Zambia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Severe Sepsis
Tuberculosis
Keywords: Sepsis
Severe sepsis
Tuberculosis
Bundle
Zambia
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Fogarty International Center of the National Institute of Health
First posted: 2012-08-13
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: In-hospital all cause mortality
timeFrame: During hospitalization, expected average 14 days
Secondary outcomes:
measure: 28-day all-cause mortality
timeFrame: 28-day
measure: In-hospital all cause mortality adjusted for illness severity
timeFrame: During hospitalization, expected average 14 days
measure: 28-day all cause mortality adjusted for baseline illness severity
timeFrame: 28-day
measure: Cumulative adverse events
timeFrame: During hospitalization, expected average 14 days
measure: Treatment cost per patient
timeFrame: During hospitalization, expected average 14 days
measure: Antibiotic changed due to culture results
timeFrame: During hospitalization, expected average 14 days
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: Vanderbilt University and University of Zambia
name: Benjamin L Andrews, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.