Abstract
Background: Across sub-Saharan Africa, blood supplies are threatened by numerous pathogens. In some locations, Plasmodium parasitemia prevalence in donor blood is nearly 50%. Donor testing for malaria in these areas is not effective and the risk of transfusion-transmitted malaria (TTM) is high. The Mirasol® PRT System for Whole Blood (WB) is a medical device intended for extracorporeal pathogen reduction of WB. The current clinical study evaluated the ability of Mirasol-treated WB to reduce the incidence of TTM.
Study Design/Methods: This was a prospective, randomized, double-blind, controlled, single-center study in Ghana, which is hyperendemic for malaria. The study had 90% power to demonstrate a 90% reduction in TTM. Hospitalized patients requiring WB transfusions were randomly allocated to receive ≤ 2 transfusions of standard (untreated) or Mirasol-treated WB. The primary endpoint was the incidence of TTM as measured by quantitative polymerase chain reaction and Plasmodium alleleic sequence homology between transfused and patient WB during 28 days of follow-up. Patient safety was assessed by monitoring treatment-emergent adverse events (TEAEs) and transfusion reactions.Clinical outcomes related to hemoglobin increments, hemostatic parameters, and clinical chemistries were monitored for 28 days post-transfusion.
Results: Overall, 226 subjects (113 Mirasol, 113 Untreated) were enrolled; 223 subjects were included in the safety analysis. Sixty-five (65) subjects were non-parasitemic at pre-transfusion (28 Mirasol, 37 Untreated) and received at least 1 parasitemic WB transfusion. Of 16 cases of suspected TTM (3 Mirasol, 13 Untreated) with 2 consecutive days of parasitemia, 9 were confirmed by alleleic homology (1 Mirasol, 8 Untreated). Incidence of TTM was significantly reduced in patients receiving treated products. Hemoglobin (mean [standard deviation]) was similar between groups at baseline (6.71 g/dL; p = 1.0), and Day 1 following 1 transfusion (8.53 [2.0] vs 8.49 [1.5] g/dL; p = 0.93) or 2 transfusions (7.09 [1.5] vs 7.38 [1.6] g/dL; p = 0.33). Ninety-two subjects (48 Mirasol, 44 Untreated) reported 145 TEAEs (75 Mirasol, 70 Untreated). Transfusion reactions were observed in 8.1% and 13.4% of subjects receiving Mirasol-treated and untreated WB, respectively.
Table. Incidence of TTM Mirasol n (%); 95% CI Untreated n (%); 95% CI P-Value 2 Consecutive days of ParasitemiaN = 65 3 (10.7); 2.3, 28.2 n = 28 13 (35.1); 20.2, 52.2n = 37 < 0.05 2 Consecutive days of Parasitemia and >2 Allele match by PCRN = 65 1 (3.6); 0.1, 18.3n = 28 8 (21.6); 9.8, 38.2n = 37 < 0.05 ITT PopulationN = 223 1 (0.9); 0.0, 4.9n = 111 8 (7.1); 3.1, 13.6n = 112 < 0.05 Abbreviation: CI = confidence interval, ITT = intent-to-treat, PCR = polymerase chain reaction.
Conclusions: The primary endpoint of the study was met. Mirasol treatment of WB clinically and statistically reduced TTM infections in the study population. This was the first human clinical study demonstrating that a PRT system can reduce transmission of a bloodborne pathogen. No safety issues were related to the device or device-treated WB. Transfusion reactions did not differ between patients receiving Mirasol-treated or untreated WB. Hemoglobin increments and transfusion outcome parameters in transfused patients did not differ between the treatment groups.
Disclosures
Allain: Terumo BCT: Consultancy. Owusu-Ofori:Terumo BCT: Other: Clinical Study Sub-Investigator. Marschner:Terumo BCT: Employment. Goodrich:Terumo BCT: Employment. Owusu-Ofori:Terumo BCT: Other: Clinical Study Investigator.
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