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V. Brixner et al.
Table 6. Adverse events (based on intention-to-treat analysis).
Any adverse events*
Related to platelet transfusion
Rate per transfusion episode and patient Unrelated to platelet transfusion
Non-serious adverse events Related to platelet transfusion
Rate per transfusion episode and patient
Unrelated to platelet transfusion Grade 1 or 2 adverse events
Related to platelet transfusion
Rate per transfusion episode and patient
Unrelated to platelet transfusion
Grade 3 or 4 adverse events
Related to platelet transfusion Unrelated to platelet transfusion
Serious adverse events
Related to platelet transfusion Unrelated to platelet transfusion
Patients with severe bleeding (WHO grades 3 and 4)
Death n (%)
n
n (%) mean n (%) n (%) n (%) Mean n (%) n (%) n (%) mean n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) 2 (2.30)
UVC
741
34 (4.59) 0.09 707 (95.41) 731 (98.65) 34 (4.65) 2.69 697 (95.35) 617 (84.40) 33 (5.35) 0.09 584 (94.65) 114 (15.60) 1 (0.88) 113 (99.12) 10 (1.35) 0 (0.00) 10 (100.00) 0 (0.00) 2 (2.38)
Control
633
11 (1.74) 0.05 622 (98.26) 623 (98.42) 11 (1.77) 3.38 612 (98.23) 510 (81.86) 10 (1.96) 0.03 500 (98.04) 113 (18.14) 1 (0.88) 112 (99.12) 10 (1.58) 0 (0.00) 10 (100.00) 1 (1.19) 1.000
P
0.328 0.034 0.127 0.457 0.326 0.034 0.159 0.454 0.255 0.031 0.047 0.376 0.895 0.987 0.897
0.940 0.491
*The causal relationship of an adverse event to a platelet transfusion was classified by the investigators using the imputability levels ‘excluded’,‘unlikely’,‘possible’,‘likely/prob- able’, and ‘certain’. Adverse events classified as ‘excluded’ or ‘unlikely’ were considered as unrelated, while adverse events classified as ‘possible’,‘likely/probable’ or ‘certain’ were considered as related.UVC:ultrviolet C;WHO:World Health Organisation.
this and other transfusion studies with new platelet prod- ucts that a consensual non-inferiority margin does not exist. Other trials with pathogen-reduced platelets using the 1-hour CCI as primary endpoint set different non-infe- riority margins (e.g., 20% for the MIRACLE trial).19 However, the suitability of bleeding as efficacy outcome in non-inferiority clinical trials with pathogen-reduced platelets is also under debate.35 It is a general limitation for clinical trials with pathogen-reduced products that testing the impact of a PR method on blood safety is unfeasible due to the extremely low frequency of infectious trans- missions. Nevertheless, the decision to implement a pathogen-reduced product will have to be based on the balance of increased safety for established and emerging pathogens and clinical efficacy, which may be influenced by PR treatment. Randomized controlled trials are gener- ally limited to small numbers of patients and usually focus on patient groups with defined demographic characteris- tics and treatment indications. In addition, results regard- ing prophylactic platelet transfusion in adult patients with thrombocytopenia and hematologic diseases are no sub- stitute for clinical studies of pathogen-reduced platelets in pediatric medicine and other clinical contexts, such as post-traumatic coagulopathy. Only postmarketing studies collecting clinical information from standard medical prac- tice in a large number and wide range of patients receiving pathogen-reduced platelet transfusions may allow for a meaningful assessment of rare adverse effects resulting from the use of pathogen-reduced blood products.47
Disclosures
VB received grants from the Research Foundation of the German Red Cross Blood Services (Forschungsgemeinschaft der Blutspendedienste des Deutschen Roten Kreuzes) and
Macopharma for the development of the UVC-based PI technol- ogy for platelets and from CERUS for a clinical trial on PI tech- nology for Red Blood Cells. GB received departmental research funding from Novartis, travel grants from Celgene, Gilead, Neovii and Sanofi and honoraria for advisory board member- ships for Celgene, Eurocept, Gilead, Hexal, Novartis, Pfizer and Jazz. PP received grants from the Research Foundation of the German Red Cross Blood Services (Forschungsgemeinschaft der Blutspendedienste des Deutschen Roten Kreuzes) and Macopharma for the development of the UVC-based PI technol- ogy for platelets. JC received consultancy fee from Pfizer, Merck, Ipsen, Medac; speaker’s bureau fees from Pfizer, Merck, Ipsen, Medac; served as consultant for Pfizer, Merck, Ipsen, Medac; received research funding from Ipsen, Medac; reports member- ship of the Federal Joint Committee (G-BA) Public Policy and Strategy Committee (non-profit). UR received department hono- raria for advisory board memberships for Pfizer, Daiichi-Sankyo, Jazz, Servier and Novartis. NA received speaker’s bureau fees from Basilea Pharmaceutica, honoraria for advice from Gilead, MSD Sharp & Dohme GmbH, Pfizer, Amgen and travel grants from Gilead, MSD Sharp & Dohme GmbH, Pfizer, Amgen. RP received consulting fee from Sanofi Genzyme and Pfizer, and received travel and accommodation expenses from Bristol-Myers Squibb. TT received personal fees from Bristol Myers Squibb, Bayer, Daichii Sankyo, Pfizer, Novo Nordisk, Chugai Pharma and Novartis. THM received grants from the Research Foundation of the German Red Cross Blood Services (Forschungsgemeinschaft der Blutspendedienste des Deutschen Roten Kreuzes) and Macopharma for the development of the UVC-based PI technology for platelets, and reports membership for advisory boards (non-profit) for three German Blood Services (Jena, Rostock, Suhl). AS received grants from the Research Foundation of the German Red Cross Blood Services (Forschungsgemeinschaft der Blutspendedienste des Deutschen
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