Supplemental Digital Content 5: Adverse reactions
The safety report was yearly prepared with the data provided by Dynamic Solutions (CRO) as required by Farmacovigilance Department. Data were compiled by monitors belonging both to Farmacovigilance (Dirección Técnico Farmacéutica) and Medical Affairs Departments of BBraun Spain S.L. and evaluation of the data plus risk-benefit assessment was issued by Safety Committee: Dr. Abelardo García de Lorenzo y Mateos (Intensive Care Unit Hospital Universitario La Paz), Head of Safety Monitoring and Follow-up and Dr. Carmen Sánchez- Álvarez and Dr. Ángel Rodríguez-Pozo. Rules for defining ands stopped the study were accorded before the beginning of the study and were approved by the Spanish Drug Agency, as communicated in the trial protocol, Final Version 2.0 (Database Management, March 30, 2006).
In order to harmonize the reporting of AEs among centers and investigators, a practice guide was developed consisting of the following checklist of expected complications that were considered non-severe in critically ill patients admitted to the ICU:
Hemoglobin < 7 g/dl
Platelets < 50,000 cells/mm3 or > 350,000 cells/mm3
Leucocytes < 2,000 cells/mm3 or > 20,000 cells/mm3
INR > 1.4
AST ≥ 76 U/l (twice the normal value)
ALT ≥ 82 U/l (twice the normal value)
Alkaline phosphatase ≥ 258 UI/L (twice the normal value)
γ-GT ≥ 100 U/l (twice the normal value)
Total bilirubin > 3.5 mg/dl
Creatinine > 3.5 mg/dl
Glycemia < 60 mg/dl or > 250 mg/dl
Calcium < 8 mg/dl or > 11 mg/dl
Phosphate < 2 mg/dl or > 6 mg/dl
Magnesium < 1.6 mg/dl or > 3.4 mg/dl
Triglycerides > 350 mg/dl
Allergic reactions
Nausea
Vomiting
Rubor
Erythema
Other adverse reactions
Adverse events
A total of 608 adverse events (AEs) was reported between December 15, 2006 and March 31, 2011 in 143 patients, 71 patients in the control group (91 %) and 72 patients in the treatment group (89 %). 24 AEs were assessed as treatment related and therefore considered as adverse reaction (AR, 10 in the control and 14 in the treatment group). None of these ARs was classified as serious or unexpected.
Table 5-1: Overview of adverse events.
Number of adverse events
Adverse event MCT/LCT
(n=307)
MCT/LCT/FO (n=301)
Total (n=608)
INR > 1.4 17 12 29
Creatinine > 3.5 mg/dl 2 3 5
Glycemia > 250 mg/dl 3 10 13
Magnesium < 1.6 mg/dl 16 16 32
Magnesium > 3.4 mg/dl 1 2 3
Phosphate < 2 mg/dl 33 23 56
Phosphate > 6 mg/dl 4 4 8
Calcium < 8 mg/dl 41 47 88
Triglycerides > 350 mg/dl 17 16 33
AST ≥ 76 IU/l 18 23 41
ALT ≥ 82 IU/l 22 21 43
Alkaline phosphatase ≥ 258
IU/L 14 13 27
γ-GT ≥ 100 IU/l 52 53 105
Total bilirubin > 3.5 mg/dl 12 8 20
Hemoglobin < 7 g/dl 1 5 6
Leucocytes > 20,000
cells/mm3 33 19 52
Platelets < 50,000
cells/mm3 10 9 19
Platelets > 350,000
cells/mm3 13 15 28
Others 0 2 2
Figure 5-1: Distribution of the Adverse Events.
