Table 1 Comparison of (a) targeted population, (b) experimental treatments of four trials on corticosteroids for septic shock
Ger-Inf-05 | CORTICUS | APROCCHSS | ADRENALS | |
|---|---|---|---|---|
(a) | ||||
Expected sample size | 300 | 800 | 1240 | 3800 |
Actual sample size | 300 | 500 | 1241 | ? |
Time window for inclusion since onset of shock | 3 h then protocol amended for 8 h | 72 h | 24 h | 24 h |
Age | ≥18 years | ≥18 years | ≥18 years | ≥18 years |
Shock criteria | SBP < 90 mm Hg for at least 1 h despite adequate fluid replacement and >5 μg/kg/h of dopamine or epinephrine or norepinephrine; Arterial lactate >2 mmol/l | SBP < 90 mmHg or decrease >50 mmHg in SBP in previous hypertensive patients despite adequate fluid replacement or need for vasopressors to maintain SBP ≥ 90 mmHg Administration of vasopressor for ≥1 h | Norepinephrine or epinephrine at a rate ≥0.25 µg/kg/min or ≥1 mg/h) or any other vasopressor to maintain SBP ≥ 90 mmHg or MBP ≥ 65 mmHg Administration of vasopressors for ≥6 h | Vasopressors or inotropes to maintain a SBP > 90 mmHg, or MBP > 60 mmHg, or a MBP target set by the treating clinician for maintaining perfusion Administration of vasopressors or inotropes for =4 h |
Mechanical ventilation as a mandatory entry criteria | Yes | No | No | Yes |
Organ failure | Urinary output of <0.5 ml/kg for ≥1 h Or PaO2/FIO2 < 280 mmHg | Urine output <0.5 ml/kg/h for ≥1 h Or pH < 7.3, or arterial base deficit ≥5.0 mmol/l, or arterial lactate >2 mmol/l Or PaO2/FIO2 < 280 in the absence of pneumonia, and <200 in the presence of pneumonia Or platelet count ≤100,000 cells/mm3 Or Glasgow Coma Scale <14 or acute change from baseline) | Sequential Organ Failure Assessment (SOFA) score ≥3 for ≥2 organs for ≥6 consecutive hours | Not mentioned |
Non-responders to the Synacthen test as the primary subgroup of interest | Yes | Yes | Yes | No |
(b) | ||||
Type of corticosteroids | Hydrocortisone hemisuccinate and 9-α-fludrocortisone | Hydrocortisone hemisuccinate | Hydrocortisone hemisuccinate and 9-α-fludrocortisone | Hydrocortisone |
Dose per day | Hydrocortisone 200 mg Fludrocortisone 50 µg | 200 mg | Hydrocortisone 200 mg Fludrocortisone 50 µg | 200 mg |
Route of administration | Hydrocortisone: four intravenous bolus of 50 mg Fludrocortisone: 50 µg via the nasogastric tube | Four intravenous bolus of 50 mg | Hydrocortisone: four intravenous bolus of 50 mg Fludrocortisone: 50 µg via the nasogastric tube | Intravenous continuous infusion rate without loading dose |
Duration | Seven days at full dose | Five days at full dose then tapered to 50 mg intravenously every 12 h for days 6 to 8, 50 mg every 24 h for days 9 to 11, and then stopped | Seven days at full dose | Seven days at full dose, while in the ICU |