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Use of Drotrecogin alfa (activated) in Italian intensive care units: the results of a nationwide survey

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Abstract

Objective

To monitor the use of drotrecogin alfa activated (DrotAA) in Italy and its effects on patients' health.

Design

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

Setting

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.

Patients and participants

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.

Measurements and 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.

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Acknowledgements

This study was funded by the Italian Medicines Agency of the Ministry of Health (AIFA – “Agenzia Italiana del Farmaco”) and carried out in collaboration with AIFA and the “Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva” (GiViTI). GiViTI is the recipient of unconditioned grants from AstraZeneca Italy, Sanofi-Aventis Italy and Draeger Italia, none of which were involved in this study in any way. The authors substantially contributed to: conception and design (G. B., S. L., A. Ad., D. P.), analysis (G. B., C. R.) and interpretation (all authors) of data, the drafting (G. B., D. P.) or critical revision (C. R., S. L., A. Ad., A. Am.) of the article. All of them approved the final version of the manuscript. The full list of participating centres is given in the online supplement. G. Bertolini had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. GiViTI Steering Committee: N. Latronico, Brescia; M. Tavola, Lecco; D. Radrizzani, Legnano (MI); D. Giudici, M. Langer, A. Sicignano, Milan; M. Messina, Olbia; R. Tetamo, Palermo; P. Malacarne, Pisa; G. Bertolini, Ranica (BG); G. Nardi, Rome; S. Livigni, Torino; E. Nascimben, Treviso.

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Correspondence to Guido Bertolini.

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This article is discussed in the editorial available at: http://dx.doi.org/10.1007/s00134-007-0556-8

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Bertolini, G., Rossi, C., Anghileri, A. et al. Use of Drotrecogin alfa (activated) in Italian intensive care units: the results of a nationwide survey. Intensive Care Med 33, 426–434 (2007). https://doi.org/10.1007/s00134-007-0554-x

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  • DOI: https://doi.org/10.1007/s00134-007-0554-x

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