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

NCT02157259 | Completed

• 1 other identifier: SEA-050 Sepsis Study
• Study Type: observational
• Target: 2,250
• Locations: 3 countries
• Sites: 15

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.

Conditions

Sepsis; Severe Sepsis

Outcome Measures

Primary Outcomes (1)

• The etiology of community-acquired sepsis and severe sepsis expressed in percentages of enrolled subjects.

  Total length of time that subjects will be in the study is 28 to 35 days.

Secondary Outcomes (17)

• The time from hospital admission to any systemic antibiotic administration.

  2 years

• Percentage of initial systemic antimicrobial effective to treat the cause of the infection.

  2 years

• Percentage of subjects receiving fluid challenge (giving bolus of fluid) if the patient has hypotension.

  2 years

• Percentage of subjects receiving adequate ventilatory support (including percentage of subjects receiving supplemental oxygen, percentage of subjects receiving Positive-end Expiratory Pressure (PEEP).

  2 years

• Percentage of subjects receiving low-volume lung-protective ventilation.

  2 years

Eligibility Criteria

• Age: 30 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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):
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• FHI 360: collaborator
• Social & Scientific Systems Inc.: collaborator

Study Sites (15)

Dr. Sardjito Hospital

Yogyakarta, DI Yogyakarta, Indonesia

Location

Cipto Mangunkusumo Hospital

Jakarta, DKI Jaya, Indonesia

Location

Universitas Hasanuddin

Makassar, South Sulawesi, 90245, Indonesia

Location

Dr. Wahidin Soedirohusodo

Makassar, South Sulawesi, Indonesia

Location

Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Bangkok, Bangkok, Thailand

Location

Pediatric Unit Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Bangkok, Bangkok, Thailand

Location

Queen Sirikit National Institute of Child Health

Bangkok, Bangkok, Thailand

Location

Sappasitthiprasong Hospital

Ubon Ratchathani, Changwat Ubon Ratchathani, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiangrai, Chiangrai, Thailand

Location

National Hospital of Paediatric

Hanoi, Hanoi, Vietnam

Location

National Hospital of Tropical Diseases

Hanoi, Hanoi, Vietnam

Location

Children Hospital 1

Ho Chi Minh City, Ho Chi Minh City, Vietnam

Location

Children Hospital 2

Ho Chi Minh City, Ho Chi Minh City, Vietnam

Location

Hospital of Tropical Diseases

Ho Chi Minh City, Ho Chi Minh City, Vietnam

Location

Hue Central Hospital

Huế, Hue City, Vietnam

Location

Related Publications (26)

• World Health Organization (2008) The global burden of disease: 2004 update.

  BACKGROUND

• Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan;36(1):296-327. doi: 10.1097/01.CCM.0000298158.12101.41.

  PMID: 18158437 BACKGROUND

• Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM; FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011 Jun 30;364(26):2483-95. doi: 10.1056/NEJMoa1101549. Epub 2011 May 26.

  PMID: 21615299 BACKGROUND

• Cheng AC, West TE, Limmathurotsakul D, Peacock SJ. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med. 2008 Aug 19;5(8):e175. doi: 10.1371/journal.pmed.0050175.

  PMID: 18752342 BACKGROUND

• Suttinont C, Losuwanaluk K, Niwatayakul K, Hoontrakul S, Intaranongpai W, Silpasakorn S, Suwancharoen D, Panlar P, Saisongkorh W, Rolain JM, Raoult D, Suputtamongkol Y. Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study. Ann Trop Med Parasitol. 2006 Jun;100(4):363-70. doi: 10.1179/136485906X112158.

  PMID: 16762116 BACKGROUND

• Gasem MH, Wagenaar JF, Goris MG, Adi MS, Isbandrio BB, Hartskeerl RA, Rolain JM, Raoult D, van Gorp EC. Murine typhus and leptospirosis as causes of acute undifferentiated fever, Indonesia. Emerg Infect Dis. 2009 Jun;15(6):975-7. doi: 10.3201/eid1506.081405.

  PMID: 19523308 BACKGROUND

• Phongmany S, Rolain JM, Phetsouvanh R, Blacksell SD, Soukkhaseum V, Rasachack B, Phiasakha K, Soukkhaseum S, Frichithavong K, Chu V, Keolouangkhot V, Martinez-Aussel B, Chang K, Darasavath C, Rattanavong O, Sisouphone S, Mayxay M, Vidamaly S, Parola P, Thammavong C, Heuangvongsy M, Syhavong B, Raoult D, White NJ, Newton PN. Rickettsial infections and fever, Vientiane, Laos. Emerg Infect Dis. 2006 Feb;12(2):256-62. doi: 10.3201/eid1202.050900.

  PMID: 16494751 BACKGROUND

• Hoa NT, Diep TS, Wain J, Parry CM, Hien TT, Smith MD, Walsh AL, White NJ. Community-acquired septicaemia in southern Viet Nam: the importance of multidrug-resistant Salmonella typhi. Trans R Soc Trop Med Hyg. 1998 Sep-Oct;92(5):503-8. doi: 10.1016/s0035-9203(98)90891-4.

  PMID: 9861362 BACKGROUND

• Wijedoru LP, Kumar V, Chanpheaktra N, Chheng K, Smits HL, Pastoor R, Nga TV, Baker S, Wuthiekanun V, Peacock SJ, Putchhat H, Parry CM. Typhoid fever among hospitalized febrile children in Siem Reap, Cambodia. J Trop Pediatr. 2012 Feb;58(1):68-70. doi: 10.1093/tropej/fmr032. Epub 2011 Apr 20.

  PMID: 21508082 BACKGROUND

• Suputtamongkol Y, Hall AJ, Dance DA, Chaowagul W, Rajchanuvong A, Smith MD, White NJ. The epidemiology of melioidosis in Ubon Ratchatani, northeast Thailand. Int J Epidemiol. 1994 Oct;23(5):1082-90. doi: 10.1093/ije/23.5.1082.

  PMID: 7860160 BACKGROUND

• Limmathurotsakul D, Wongratanacheewin S, Teerawattanasook N, Wongsuvan G, Chaisuksant S, Chetchotisakd P, Chaowagul W, Day NP, Peacock SJ. Increasing incidence of human melioidosis in Northeast Thailand. Am J Trop Med Hyg. 2010 Jun;82(6):1113-7. doi: 10.4269/ajtmh.2010.10-0038.

  PMID: 20519609 BACKGROUND

• Bhengsri S, Baggett HC, Jorakate P, Kaewpan A, Prapasiri P, Naorat S, Thamthitiwat S, Tanwisaid K, Chantra S, Salika P, Dejsirilert S, Peruski LF, Maloney SA. Incidence of bacteremic melioidosis in eastern and northeastern Thailand. Am J Trop Med Hyg. 2011 Jul;85(1):117-20. doi: 10.4269/ajtmh.2011.11-0070.

  PMID: 21734135 BACKGROUND

• Hashairi F, Hasan H, Azlan K, Deris ZZ. An eight-year review of blood culture and susceptibility among sepsis cases in an emergency department in Northeastern Malaysia. Trop Biomed. 2011 Dec;28(3):599-605.

  PMID: 22433889 BACKGROUND

• Deen J, von Seidlein L, Andersen F, Elle N, White NJ, Lubell Y. Community-acquired bacterial bloodstream infections in developing countries in south and southeast Asia: a systematic review. Lancet Infect Dis. 2012 Jun;12(6):480-7. doi: 10.1016/S1473-3099(12)70028-2.

  PMID: 22632186 BACKGROUND

• Angkasekwinai N, Rattanaumpawan P, Thamlikitkul V. Epidemiology of sepsis in Siriraj Hospital 2007. J Med Assoc Thai. 2009 Mar;92 Suppl 2:S68-78.

  PMID: 19562989 BACKGROUND

• Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73. doi: 10.1097/01.ccm.0000117317.18092.e4.

  PMID: 15090974 BACKGROUND

• Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, Gomersall CD, Faruq MO, Shrestha BR, Gia Binh N, Arabi YM, Salahuddin N, Wahyuprajitno B, Tu ML, Wahab AY, Hameed AA, Nishimura M, Procyshyn M, Chan YH; MOSAICS Study Group. Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ. 2011 Jun 13;342:d3245. doi: 10.1136/bmj.d3245.

  PMID: 21669950 BACKGROUND

• Khwannimit B, Bhurayanontachai R. The epidemiology of, and risk factors for, mortality from severe sepsis and septic shock in a tertiary-care university hospital setting. Epidemiol Infect. 2009 Sep;137(9):1333-41. doi: 10.1017/S0950268809002027. Epub 2009 Feb 4.

  PMID: 19192320 BACKGROUND

• Kanoksil M, Jatapai A, Peacock SJ, Limmathurotsakul D. Epidemiology, microbiology and mortality associated with community-acquired bacteremia in northeast Thailand: a multicenter surveillance study. PLoS One. 2013;8(1):e54714. doi: 10.1371/journal.pone.0054714. Epub 2013 Jan 18.

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  PMID: 12648838 BACKGROUND

• Personal communication with Professor Jeremy Farrar, Director, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.

  BACKGROUND

• West TE CN, Chierakul W, Limmathurotsakul D, Wuthiekanun V, Myers ND, Emond MJ, Wurfel MM, Hawn TR, Peacock SJ, Skerrett SJ. A hypofunctional TLR5 is genetic variant is associated with survival in meliodosis. 2011

  BACKGROUND

• Lie KC, Lau CY, Van Vinh Chau N, West TE, Limmathurotsakul D; for Southeast Asia Infectious Disease Clinical Research Network. Utility of SOFA score, management and outcomes of sepsis in Southeast Asia: a multinational multicenter prospective observational study. J Intensive Care. 2018 Feb 14;6:9. doi: 10.1186/s40560-018-0279-7. eCollection 2018.

  PMID: 29468069 DERIVED

• Southeast Asia Infectious Disease Clinical Research Network. Causes and outcomes of sepsis in southeast Asia: a multinational multicentre cross-sectional study. Lancet Glob Health. 2017 Feb;5(2):e157-e167. doi: 10.1016/S2214-109X(17)30007-4.

  PMID: 28104185 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Direk Limmathurotsakul, MD

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: June 5, 2014
• Study Start: December 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 18, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will share

Locations

VN (6); ID (4); TH (5)