Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial

Abstract

The overall safety profile of PCT PLTs was comparable to untreated PLTs.

Determination of acute lung injury after repeated platelet transfusions

“…In contrast to the low incidence of ALI (5/645, 0.8%) reported by the clinical investigators during conduct of the clinical trial, 13 the EPP review using AECC criteria observed a higher frequency of ALI (35/645, 5.4%). We believe this difference was due to the use of specific criteria for the diagnosis of ALI, including ARDS, by the expert panel and the lack of a specific code for ALI in the MedDRA coding dictionary used in the initial clinical trial.…”

“…AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) terminology (version 3.3) to Preferred Term (PT) and mapped to the primary and nonprimary respiratory, thoracic, and mediastinal disorders System Organ Class (SOC), and the frequencies of the respective AEs were calculated (supplemental Figure 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). 13 No PT for ALI was available in version 3.3 of MedDRA. During the conduct of the SPRINT trial, investigators were not provided with specific per-protocol criteria for the diagnosis of ALI or ARDS.…”

“…14 The frequencies of AEs at the PT level and summarized by SOC were determined as part of the analysis of safety. 13 Fisher exact test was used to test for treatment differences for categorical data with 2-sided P values with a 5% significance level. 12,13 No statistically significant differences were observed between Test and Reference groups for grade 3 and 4 AEs overall and in the MedDRA respiratory, thoracic, and mediastinal disorders SOC.…”

“…13 Fisher exact test was used to test for treatment differences for categorical data with 2-sided P values with a 5% significance level. 12,13 No statistically significant differences were observed between Test and Reference groups for grade 3 and 4 AEs overall and in the MedDRA respiratory, thoracic, and mediastinal disorders SOC. However, statistically significant differences between groups were observed for 3 low-frequency AEs at the PT level: ARDS (5/318 [1.6%] Test vs 0/327 Reference, P ϭ .029), pneumonia not otherwise specified (7/318 [2.2%] Test vs 0 Reference, P ϭ .007), and pleuritic pain (12/318 [3.8%] Test vs 3/327 [0.9%] Reference, P ϭ .018).…”

“…However, statistically significant differences between groups were observed for 3 low-frequency AEs at the PT level: ARDS (5/318 [1.6%] Test vs 0/327 Reference, P ϭ .029), pneumonia not otherwise specified (7/318 [2.2%] Test vs 0 Reference, P ϭ .007), and pleuritic pain (12/318 [3.8%] Test vs 3/327 [0.9%] Reference, P ϭ .018). 13 As a result of the unexpectedly low frequency of ARDS, and the lack of a MedDRA coding term for ALI in version 3.3, a retrospective review and analysis of patients with potential CSPAEs using specific diagnostic criteria for ALI, including the subset of ARDS, was conducted to determine more precisely the frequency of ALI in the P3A99 trial.…”