An Observational Study of the Causes, Management, and Outcomes of Community-acquired Sepsis and Severe Sepsis in Southeast Asia

The study will enroll 2,250 total patients with sepsis or severe sepsis patients up to 2 years of study. 750 patients will be enrolled in each of Thailand, Vietnam, and Indonesia. There will be 3 sites in each country and some sites will function as cluster/unit sites linking up to 3 hospitals as one 'site' to enable adequate enrollment of both adult and pediatric cases.

Primary objective of the study is to determine the causes of community-acquired sepsis and severe sepsis in adult and pediatric subjects across Southeast Asia.

The secondary objectives are as follow:

• To define the current acute management (within the first 48 hours after admission) of subjects presenting with community-acquired sepsis and severe sepsis and gaps of current practice as defined by the surviving sepsis campaign 2012. This will provide the basis for designing practical interventions to reduce the mortality of subjects with sepsis and severe sepsis in the future.
• To define the clinical outcomes of community-acquired sepsis and severe sepsis in Southeast Asia.
• To identify risk factors associated with sepsis or severe sepsis.
• To determine the extent of antimicrobial resistance in organisms that cause community-acquired sepsis and severe sepsis in Southeast Asia and to determine the association between antimicrobial resistance and mortality.
• To evaluate the accuracy of selected rapid diagnostic tests (RDTs) in determining the causes of community-acquired sepsis and severe sepsis compared to well-defined gold standard tests.

As this is an observational study and not a clinical trial, researchers will not be involved in the management, care and treatment of study subjects. This will remain the responsibility of the attending medical staff according to standard of care (SOC) in the participating hospitals. Therefore the research study will not influence patient management. SOC for sepsis and severe sepsis in each subject will be recorded, and will be reported as summary statistics at the end of the study. This will not be used to influence the management and care of sepsis and severe sepsis cases at the participating hospitals during the study period, but will be used to guide the improvement of the SOC after the study is complete.

NOTE: EACH INSTITUTION IN THIS STUDY IS ITS OWN SPONSOR AS LISTED BELOW:

• Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
• Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
• Children's Hospital 1 Ho Chi Minh City, Vietnam.
• Children's Hospital 2 Ho Chi Minh City, Vietnam.
• Hospital for Tropical Diseases Ho Chi Minh City, Vietnam.
• National Hospital for Pediatrics Hanoi, Vietnam.
• National Hospital for Tropical Diseases, Hanoi, Vietnam.
• Hue Central Hospital, Hue City, Vietnam.
• Dr. Wahidin Soedirohusodo Hospital Makassar, Indonesia.
• Dr. Sardjito Hospital Yogyakarta, Indonesia.
• Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
• Sappasithiprasong Hospital Ubonratchathani, Thailand
• Chiangrai Prachanukroh Hospital, Chiangrai Thailand
• University of Oxford, United Kingdom

Inclusion criteria

• Age ≥30 days old and weighing at least 3 kg or more on the day of enrollment into the study
• Required hospitalization as decided by the attending physician
• Documented by attending physician that an infection is the primary cause of illness leading to the hospitalization. These can be infections due to any pathogens (bacteria, viruses, fungi and parasites).
• Presence of Systemic Inflammatory Response Syndrome (SIRS):

4.1 For adults (≥ 18 years old), any combination of a minimum of any 3 of the following 20 parameters

• Fever or hypothermia (Core body temperature defined as >38.3 C or <36.0 C)
• Tachycardia (heart rate >90 beats per minute)
• Tachypnea (respiratory rate >20 per minute)
• Arterial hypotension (systolic blood pressure (SBP) <90 mmHg, mean arterial pressure (MAP) <70 mmHg, or SBP decrease >40 mmHg)
• White blood cell (WBC) >12,000 u/L or <4000 u/L or immature forms >10%
• Platelet count <100,000 u/L
• Altered mental status with Glasgow Coma Score (GCS) <15
• Hypoxemia (Pulse Oximetry Level <95)
• Ileus
• Significant edema or positive fluid balance
• Decreased capillary refill or mottling
• Hyperglycemia (plasma glucose >140 mg/dL) in the absence of diabetes
• Plasma C-reactive protein >2 SD above the normal value
• Plasma procalcitonin > 2 SD above the normal value
• Arterial hypoxemia (PaO2 / FIO2 <300)
• Acute oliguria (urine output <0.5 mL/kg/hr or 45 mmol/L for 2 hours)
• Creatinine increase >0.5 mg/dL
• INR >1.5 or a PTT >60 seconds
• Plasma total bilirubin >4 mg/dl or 70 mmol/L
• Hyperlactatemia (>1 mmol/L)

4.2 For pediatric patients (>30 days old and <18 years old), all of the 3 following symptoms:

• Fever or hypothermia (rectal temperature defined as >38.5 C or <35.0 C [or equivalent])
• Tachycardia (heart rate >2 SD above the normal value for age). This could be absent in hypothermic subject.
• Tachypnea (respiratory rate >2 SD above the normal value for age)

AND at least one of the following parameters:

• Altered mental status,(e.g., drowsiness, poor quality of cry, poor reaction to parent stimuli, and poor response to social overtures)
• Systolic blood pressure <2 SD below the normal value for age OR narrow pulse pressure (<20 mmHg) OR poor perfusion (capillary refill >2 sec)
• Hypoxemia (Pulse Oximetry Level <95)
• White blood cell >15,000 u/L or <5,000 u/L or immature forms >10%.
• Informed Consent has been obtained.

Exclusion criteria

• Admitted to the study site hospital for this current episode for more than 24 hours before enrollment.
• Hospitalized for this current episode for more than 72 hours at another primary/referring hospital.
• Prior to this current episode, the subject was admitted to any hospital within the last 30 days.
• An underlying pre-existing condition is thought to have led to or contributed to this sepsis episode. For example, sepsis is considered to be directly attributable to existing non-infectious conditions such as stroke, cardiovascular diseases, acute myocardial infarction, cancer, burn, injury, and trauma.
• Prior to enrollment, it is documented by the attending physician that hospital acquired infection is associated with the cause of the sepsis or severe sepsis.
• The subject has been enrolled into this study or another sepsis study before.