The Mirasol Evaluation of Reduction in Infections Trial (MERIT): study protocol for a randomized controlled clinical trial

Abstract

Background Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8). Methods MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated. Discussion Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda. Trial registration Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669. Registered on 9 November 2018

SARS‐CoV‐2 seroprevalence among blood donors in Uganda: 2019–2022

“…All donors are screened for serological evidence of the four major TTIs using an ARCHITECT (Abbott) platform: human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum (syphilis). As part of the MERIT, additional blood is collected in ethylenediamine tetraacetic acid (EDTA) tubes from the diversion pouch for further testing 13 . MERIT samples were collected from October 2019 to April 2022 in Kampala, Uganda, separated into plasma and red cell pellets, and stored at −80°C until testing.…”

“…Samples were collected as a part of the Mirasol Evaluation of Reduction in Infections Trial (MERIT), a randomized clinical trial located in Uganda investigating the effect of a riboflavin plus UV light pathogen reduction technology on the incidence of transfusion transmitted infections (TTIs). 13 The Ugandan Blood Transfusion Services (UBTS), which is responsible for all blood collections in Uganda, 14,15 collects approximately 300,000 units of blood a year. UBTS supplies fresh nonleukocyte-reduced whole blood units for MERIT and only collects blood from voluntary nonremunerated donors.…”

“…As part of the MERIT, additional blood is collected in ethylenediamine tetraacetic acid (EDTA) tubes from the diversion pouch for further testing. 13 MERIT samples were collected from October 2019 to April 2022 in Kampala, Uganda, separated into plasma and red cell pellets, and stored at À80°C until testing. In November-December 2021, additional samples were collected from blood donors to assess SARS-CoV-2 seroprevalence from a broader geographic range of four districts in Uganda (Kampala, Jinja, Masaka, and Hoima).…”

Survey of blood collection and transfusion practices among institutions in Africa

“…Further, prior authors have suggested the utility of PRT in various countries in Africa given the high prevalence of transfusion-transmitted infections (TTI), reliance on high-risk donors, and suboptimal testing. [15][16][17] Notably, some institutions reported collecting blood onsite from patients themselves, with many relying on rapid diagnostic tests (RDTs) for infectious disease screening, despite their inadequate sensitivity to particular infectious agents. [18][19][20][21][22][23][24] This high utilization of RDTs, which are generally accepted to not be ideal for TTI testing, [18][19][20][21][22][23][24] is likely secondary to a lack of other feasible options.…”

“…25,27 To introduce more sensitive detection methods would increase costs dramatically and further reduce the donor pool. 25 This constellation of results indicates further studies are needed to assess barriers to implementation of PRT, 17 areas for improvement in infectious disease screening, and how blood donors are selected.…”