Clinical trial NCT02157259: An Observational Study of the Causes, Management, and Outcomes of Community-acquired Sepsis and Severe Sepsis in Southeast Asia
Official title: An Observational Study of the Causes, Management, and Outcomes of Community-acquired Sepsis and Severe Sepsis in Southeast Asia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Severe Sepsis
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: FHI 360
name: Social & Scientific Systems Inc.
First posted: 2014-06-05
Enrollment: 2250
Sex: ALL
Minimum age (years): 30
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Male and female patients, age 30 days on the day of enrollment with community-acquired sepsis or severe sepsis in Southeast Asia. Of the 2,250 enrolled patients, 1,125 will be adults and 1,125 will be children.

Brief summary: This is an observational study to identify the etiology, management, and outcome of community-acquired sepsis and severe sepsis in children and adults in Southeast Asia. The study will take place in Thailand, Vietnam, and Indonesia, the partner countries of SEAICRN. Potential study patients will be any patients (both children and adults) who are presented at the hospital with community-acquired sepsis or severe sepsis and require hospitalization.

Detailed description: 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:

1. Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
2. Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
3. Children's Hospital 1 Ho Chi Minh City, Vietnam.
4. Children's Hospital 2 Ho Chi Minh City, Vietnam.
5. Hospital for Tropical Diseases Ho Chi Minh City, Vietnam.
6. National Hospital for Pediatrics Hanoi, Vietnam.
7. National Hospital for Tropical Diseases, Hanoi, Vietnam.
8. Hue Central Hospital, Hue City, Vietnam.
9. Dr. Wahidin Soedirohusodo Hospital Makassar, Indonesia.
10. Dr. Sardjito Hospital Yogyakarta, Indonesia.
11. Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
12. Sappasithiprasong Hospital Ubonratchathani, Thailand
13. Chiangrai Prachanukroh Hospital, Chiangrai Thailand
14. University of Oxford, United Kingdom

Eligibility criteria: Inclusion Criteria:

1. Age ≥30 days old and weighing at least 3 kg or more on the day of enrollment into the study
2. Required hospitalization as decided by the attending physician
3. 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).
4. 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%.
5. 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.

Primary outcomes:
measure: The etiology of community-acquired sepsis and severe sepsis expressed in percentages of enrolled subjects.
timeFrame: Total length of time that subjects will be in the study is 28 to 35 days.
Secondary outcomes:
measure: The time from hospital admission to any systemic antibiotic administration.
timeFrame: 2 years
measure: Percentage of initial systemic antimicrobial effective to treat the cause of the infection.
timeFrame: 2 years
measure: Percentage of subjects receiving fluid challenge (giving bolus of fluid) if the patient has hypotension.
timeFrame: 2 years
measure: Percentage of subjects receiving adequate ventilatory support (including percentage of subjects receiving supplemental oxygen, percentage of subjects receiving Positive-end Expiratory Pressure (PEEP).
timeFrame: 2 years
measure: Percentage of subjects receiving low-volume lung-protective ventilation.
timeFrame: 2 years
measure: Percentage of subjects receiving arterial blood gas evaluation).
timeFrame: 2 years
measure: Percentage of subjects receiving renal replacement therapies (including hemodialysis and peritoneal dialysis).
timeFrame: 2 years
measure: Percentage of subjects receiving imaging to determine source or deep foci of infection (including chest radiography, ultrasonogram, CT scan and MRI).
timeFrame: 2 years
measure: Percentage of subjects receiving evaluation by scoring system.
timeFrame: 2 years
measure: Percentage of subjects receiving stress prophylaxis.
timeFrame: 2 years
measure: Percentage of patients receiving deep vein thrombosis (DVT) prophylaxis.
timeFrame: 2 years
measure: Percentage of subjects receiving treatment in ICUs.
timeFrame: 2 years
measure: 28-day mortality rate.
timeFrame: 2 years
measure: Percentage of subjects developing major organ dysfunction; for example ventilatory failure and renal failure.
timeFrame: 2 years
measure: Risk factors associated with sepsis or severe sepsis
timeFrame: 2 years
measure: Prevalence of antimicrobial resistance and its association with appropriate empirical therapy and outcomes.
timeFrame: 2 years
measure: Sensitivities and specificities of selected RDTs in determining the causes of community-acquired sepsis and severe sepsis
timeFrame: 2 years
Other outcomes:
Locations:
city: Yogyakarta
country: Indonesia
facility: Dr. Sardjito Hospital
state: DI Yogyakarta
city: Jakarta
country: Indonesia
facility: Cipto Mangunkusumo Hospital
state: DKI Jaya
city: Makasar
country: Indonesia
facility: Dr. Wahidin Soedirohusodo
state: Sulawesi Selatan
city: Makassar
country: Indonesia
facility: Universitas Hasanuddin
state: Sulawesi Selatan
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
city: Bangkok
country: Thailand
facility: Pediatric Unit Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
city: Bangkok
country: Thailand
facility: Queen Sirikit National Institute of Child Health
city: Chiangrai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
city: Ubon Ratchathani
country: Thailand
facility: Sappasitthiprasong Hospital
city: Hanoi
country: Vietnam
facility: National Hospital of Paediatric
city: Hanoi
country: Vietnam
facility: National Hospital of Tropical Diseases
city: Ho Chi Minh City
country: Vietnam
facility: Children Hospital 1
city: Ho Chi Minh City
country: Vietnam
facility: Children Hospital 2
city: Ho Chi Minh City
country: Vietnam
facility: Hospital of Tropical Diseases
city: Hue City
country: Vietnam
facility: Hue Central Hospital
Study officials:
affiliation: Mahidol Oxford Tropical Medicine Research Unit
name: Direk Limmathurotsakul, MD
role: PRINCIPAL_INVESTIGATOR
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