GCIV as an Adjuvant Therapy for Community-Acquired Severe Sepsis or Septic Shock

• All cause mortality [ Time Frame: 7th day ] [ Designated as safety issue: Yes ]
• Course of SOFA subscores [ Time Frame: 5 Times: D-1, D1, D3, D5, D7 ] [ Designated as safety issue: Yes ]
• Laboratory Test [ Time Frame: 7th Day ] [ Designated as safety issue: Yes ]
  sputum culture test, CBC, blood chemistry, blood coagulation test, CRP, ABGA
• Duration of ICU and general ward admission [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

• Mortality [ Time Frame: 7th day ] [ Designated as safety issue: Yes ]
• Course of SOFA subscores [ Time Frame: 5 Times: D-1, D1, D3, D5, D7 ] [ Designated as safety issue: Yes ]
• Laboratory Test [ Time Frame: 7th Day ] [ Designated as safety issue: Yes ]
  sputum culture test, CBC, blood chemistry, blood coagulation test, CRP, ABGA
• Duration of ICU and general ward admission [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

This study is to determine whether the intravenous application of 'Ⅳ-Globulin S inj. (Human Immunoglobulin G)' can reduce mortality in patients with severe sepsis or septic shock.

A Placebo-controlled, Randomized, Double-blind, Multi-center, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Administration of 'IV-Globulin S inj.(Human Immunoglobulin G)' as an Adjuvant Therapy in Adult Subjects with Community-Acquired Severe Sepsis or Septic Shock.

• Severe Sepsis
• Septic Shock

• Experimental: Imunoglobulin G
  The enrolled patients will be randomized to receive supplementation of IVIG in ICU within 48 hours after hospital arrival admission for 3 consecutive days.
  Intervention: Drug: Immunoglobulin G
• Placebo Comparator: Placebo control
  The enrolled patients will be randomized to receive supplementation of placebo (0.9% NaCl) in ICU within 48 hours after hospital arrival admission for 3 consecutive days.
  Intervention: Drug: Immunoglobulin G

Inclusion Criteria:

• Patients with severe sepsis or septic shock, if all of the following criteria is satisfied.

  1. Age ≥ 18 years
  2. Proved or suspected infection in at least one site
• pneumonia
• urinary tract infection
• intra-abdominal infection
• primary bloodstream infection
• skin and soft tissue infection 3. Three or more of the following
• a core temperature ≥ 38° C or ≤ 36° C
• a heart rate ≥ 90 beats/min
• a respiratory rate ≥ 20 breaths/min or PaCO2 ≤ 32 mmHg or use of mechanical ventilation for an acute process
• a white blood cell count ≥ 12000/mm3 or ≤ 4000/ mm3 or immature neutrophils > 10% 4. Acute organ failure in one or more of the following
• kidney
• respiratory system
• blood system
• metabolic system
• circulatory system 5. APACHE score ≥ 20 and ≤ 29 6. Patient can treatment with GCIV in ICU within at least 48 hours 7. Informed consent

Exclusion Criteria:

1. Pregnant or breast-feeding women
2. a weight > 100kg
3. discharged from the hospital at least 14 days prior to new admission
4. Transferred from another hospital staying more than 48 hours
5. allergy or shock of IVIG
6. Treated with IVIG within the 12 weeks immediately preceding enrolment in this study
7. IgA deficiency
8. Hypernatremia or hyperhydration
9. Proved or suspected HIV or AIDS patients(CD4+ <200mL)
10. Current participation in any study within the last 4 weeks
11. Do not resuscitate (DNR) status
12. Patient's death is considered imminent due to coexisting disease
13. physicians decision to exclude patients from this protocol
14. Immunocompromised patients