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Talactoferrin in Severe Sepsis: Results from the phase II/III OASIS Trial
Supplemental digital content
Appendix 1: Full inclusion and exclusion criteria
All adult (> 18 years) patients admitted to one of the participating centers who were receiving antimicrobial therapy, were able to take liquid medication by mouth or feeding tube and had an onset of severe sepsis within the previous 24 hours as defined by meeting all the following criteria were included:
A. Objective evidence of confirmed or suspected infection. Suspected infection was defined as objective clinical evidence such as: (a) neutrophils in a normally sterile body fluid; (b) perforated viscus; (c) radiographic evidence of pneumonia; (d) a syndrome associated with a high likelihood of infection (e.g., ascending cholangitis), or (e) evidence of an infecting organism such as pneumococcal antigen or Legionella antigen
B. the presence of at least three manifestations of the systemic inflammatory response syndrome (SIRS) (13) due to infection within 24 hours prior to start time of the first qualifying organ dysfunction or within 24 hours after the start time of the first qualifying organ dysfunction
C. at least one acute organ dysfunction due to sepsis, that is newly developed, and not explained by other disease processes or the effects of treatment and is ongoing at the time of randomization, defined as follows:
- Septic shock (Cardiovascular): requirement for vasopressors, despite adequate fluid resuscitation, to maintain a mean arterial blood pressure (MAP) >65 mmHg or systolic blood pressure >90 mm Hg
- Respiratory: must be mechanically ventilated and have a PaO2/FiO2 ratio ≤300 or, if the lung is the primary site of infection, a PaO2/FiO2 ratio ≤200.
- Renal: i) an absolute increase in serum creatinine of ≥0.3 mg/dL within the preceding 48 hours, or ii) a relative increase in serum creatinine ≥50% within the preceding 48 hours, or iii) a urine output <0.5 mL/kg ideal body weight/hr for ≥2 hours in the absence of known or suspected urinary tract obstruction. In the presence of pre-existing impairment
2 of renal function (defined as a serum creatinine concentration >2 times the upper limit of the normal reference range prior to the onset of sepsis), the patient should meet another organ dysfunction criteria.
- Hematologic: platelet count <80,000/mm3 or a platelet count <120,000/mm3 in association with a PT-INR >1.2
- Metabolic: serum lactate >2.0 mmol/L (or equivalent in other units) despite adequate fluid resuscitation.
Exclusion criteria included: lack of consent; pregnancy; severe congestive heart failure (NYHA class IV); end-stage liver disease as defined by Child-Pugh Class C; inclusion in another investigational clinical trial within 4 weeks of randomization; 3rd degree burns involving > 20%
of the body surface area unless occurring > 7 days prior to randomization; imminent death as assessed by the investigator or life expectancy less than 6-months from pre-existing conditions, such as cancer; known HIV infection with CD4 < 200 cells/mm3 or illnesses associated with end- stage AIDS; immunosuppressant therapy, e.g., prednisone 20 mg/day or equivalent, for > 2 weeks prior to randomization; the patient or their legal representative was not committed to providing full, aggressive, life support.
3 Table S1. Ventilator-free, organ dysfunction-free, shock-free and ICU-free days in the two
groups
Talactoferrin Placebo P value Ventilator-Free Days (VFDs)
N 115 125
Mean (SD) 19.9 (9.1) 20.2 (8.5) 0.643
Median 22.0 23.0
Organ Dysfunction-Free Days
n 115 125
Mean (SD) 18.8 (8.9) 20.0 (7.5) 0.598
Median 22.0 23.0
Shock-Free Days
n 115 125
Mean (SD) 24.2 (4.8) 25.0 (3.3) 0.251
Median 26.0 26.0
ICU-Free Days
n 115 125
Mean (SD) 16.4 (8.5) 17.0 (8.0) 0.759
Median 20.0 20.0
