Use of Drotrecogin alfa (activated) in Italian intensive care units: the results of a nationwide survey.
OBJECTIVE
To monitor the use of drotrecogin alfa activated (DrotAA) in Italy and its effects on patients' health.


METHODS
Prospective pharmaco-surveillance program with a parallel non-randomized control group.


METHODS
The Ministry of Health required all intensive care units (ICUs) using DrotAA to participate in the pharmaco-surveillance program. Our control group was formed of patients eligible for treatment with DrotAA but who had not received it.


METHODS
The data we collected included basic demographic characteristics, indications, modalities of use, adverse events, and ICU mortality. We identified potentially non-collaborating centres on the basis of data on DrotAA purchasing by hospitals.


RESULTS
From 2003 to 2006, 668 cases of treatment with DrotAA were reported. We estimate that 79.3% of all patients treated in Italy in this period were recruited. Off-label use was common. Delayed start was the main reason for off-label prescription. Bleeding during infusion occurred in 73 patients (10.9%). The ICU mortality was higher in patients with bleeding (57.5 vs. 44.9%; p=0.041). Crude ICU mortality was lower in patients receiving DrotAA than in controls (46.4 vs. 54.9%; p=0.0004); however, multivariate analysis, which adjusted for certain relevant differences, showed that DrotAA treatment was associated with higher mortality after scheduled surgery.


CONCLUSIONS
These results question the way in which the drug is used in everyday clinical practice and its efficacy in a selected subgroup, and reinforce the need for a new, independent, confirmatory trial to reassess the risk-to-benefit ratio of DrotAA.
Bertolini
Guido
G
Laboratory of Clinical Epidemiology, GiViTi Coordinating Center, Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Villa Camozzi, 24020, Ranica (Bergamo), Italy. bertolini@marionegri.it
Rossi
Carlotta
C
Anghileri
Abramo
A
Livigni
Sergio
S
Addis
Antonio
A
Poole
Daniele
D
D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D017723:Drug Utilization Review; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012449:Safety; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated