A multi‐centre study of therapeutic efficacy and safety of platelet components treated with amotosalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion

Abstract

Summary Bacteria in platelet components (PC) may result in transfusion‐related sepsis (TRS). Pathogen inactivation of PC with amotosalen (A‐PC) can abrogate the risk of TRS and hence facilitate storage to 7 d. A randomized, controlled, double‐blinded trial to evaluate the efficacy and safety of A‐PC stored for 6–7 d was conducted. Patients were randomized to receive one transfusion of conventional PC (C‐PC) or A‐PC stored for 6–7 d. The primary endpoint was the 1 h corrected count increment (CCI) with an acceptable inferiority of 30%. Secondary endpoints included 1‐ and 24‐h count increment (CI), 24‐h CCI, time to next PC transfusion, red blood cell (RBC) use, bleeding and adverse events. 101 and 100 patients received A‐PC or C‐PC respectively. The ratio of 1‐h CCI (A‐PC:C‐PC) was 0·87 (95% confidence interval: 0·73, 1·03) demonstrating non‐inferiority (P = 0·007), with respective mean 1‐h CCIs of 8163 and 9383; mean 1‐h CI was not significantly different. Post‐transfusion bleeding and RBC use were not significantly different (P = 0·44, P = 0·82 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2·2 vs. 2·3 d, P = 0·72). Storage of A‐PCs for 6–7 d had no impact on platelet efficacy.

The clinical and biological impact of new pathogen inactivation technologies on platelet concentrates

“…Interpatient variability was further complicated by the variability of the response to transfusions in a single patient; interpretation of a study becomes more complex when randomization occurs at the patient level and not at the transfusion level. Lozano et al limited their assessment to one transfusion in order to reduce this effect [76]. It is also noteworthy that only the Janetzko study [74] formally defined the incidence of bacterial contamination as a secondary outcome, although the frequency of this complication was at an order of magnitude beyond the predictive power of these studies.…”

“…The results of six phase III randomized controlled trials (RCTs) with INTERCEPT-treated PCs have been published since 2003, as well as one with MIRASOL-treated PCs [74][75][76][77][78][79]. All of the studies had at least two study arms in which one group of patients received PI PCs, while the other received standard PCs.…”

“…In the TESSI trial (Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days), Lozano et al [76] opted for an innovative study design: they compared the therapeutic efficacy of amotosalen/ UVA-treated vs. standard platelets that had been stored for 6 or 7 days. Every patient was included for only a single transfusion.…”

Implications of the US Food and Drug Administration draft guidance for mitigating septic reactions from platelet transfusions

“…Hemovigilance data demonstrate a low rate of adverse events with PR platelets, 12 and some studies fail to demonstrate increased bleeding or worse clinical outcomes for patients treated with PR platelets. 13,14 However, studies have shown an association between PR platelets and a reduction in 1-and 24-hour corrected count increments, increase in platelet refractoriness, decrease in time to next transfusion, and increase in platelet use. [15][16][17] The most recent study demonstrated a 50% increase in platelets transfused and a 25% increase in red blood cells transfused in patients receiving INTERCEPT vs control platelets.…”

Inverse probability weighted estimating equations for randomized trials in transfusion medicine

“…Treatment often includes prednisone, infusions of intravenous immunoglobulin, and platelet transfusion [7]. Platelet transfusion, however, can lead to antibody responses in recipients, and as a result, there has been considerable research directed at the development of pathogeninactivated platelet products to reduce the risks of these reactions [8][9][10][11][12][13]. This article is concerned with methodological challenges arising in the design and analysis of randomized trials directed at comparing the effectiveness of standard and pathogen inactivated platelets.…”