Personalized collection of plasma from healthy donors: A randomized controlled trial of a novel technology-enabled nomogram

Abstract

Background: Source plasma is essential to support the growing demand for plasma-derived medicinal products. Supply is short, with donor availability further limited by the coronavirus disease 2019 (COVID-19) pandemic. This study examined whether a novel, personalized, technology-based nomogram was noninferior with regard to significant hypotensive adverse events (AEs) in healthy donors.

Study design and methods: IMPACT (IMproving PlasmA CollecTion) was a prospective, multicenter, double-blinded, randomized, controlled trial carried out between January 6 and March 26, 2020, in three U.S plasma collection centers. Donors were randomly assigned to the current simplified 1992 nomogram (control) or a novel percent plasma nomogram (PPN) with personalized target volume calculation (experimental). Primary endpoint was the rate of significant hypotensive AEs. Noninferiority (NI) was tested with a margin of 0.15%. Collected plasma volume was a secondary endpoint.

Results: A total of 3443 donors (mean [SD] BMI: 32 [7.74] kg/m2 ; 65% male) underwent 23,137 donations (median [range]: 6 [1-22] per subject). Ten significant hypotensive AEs were observed (six control; four experimental), with model-based AE incidence rate estimates (95% CI) of 0.051% (0.020%-0.114%) and 0.035% (0.010%-0.094%), respectively (p = .58). NI was met at an upper limit of 0.043% versus the predefined margin of 0.15%. There was no statistical difference between total AEs (all AE types: p = .32). Mean plasma volume collected was 777.8 ml (control) versus 841.7 ml (experimental); an increase of 63.9 ml per donation (8.2%; p < .0001).

Conclusion: This trial showed that a novel personalized nomogram approach in healthy donors allowed approximately 8% more plasma per donation to be collected without impairing donor safety.

Trial registration: ClinicalTrials.gov NCT04320823.

Keywords: donor safety; nomogram; plasma; plasmapheresis; source plasma.

Conflict of interest statement

Dr. Hartmann reports being employed by and holding equity interest in Haemonetics Corp. Mr. Ragusa reports being employed by and holding equity interest in Haemonetics Corp. and holding a related patent, assigned to Haemonetics Corp. (US 2018 / 0344910 A1). Dr. Burchardt, Dr. Manukyan, Dr. Popovsky, and Dr. Leitman report consulting fees from Haemonetics Corp. Dr. Leitman's opinions do not reflect the policy of the National Institutes of Health or the Department of Health and Human Services.

© 2021 The Authors. Transfusion published by Wiley Periodicals LLC. on behalf of AABB.

Figures

FIGURE 1

Profile of the IMPACT randomized controlled trial. IMPACT, IMproving PlasmA CollecTion; ITT, intention to treat; PP, per protocol [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Collected plasma volume (%) versus total plasma volume for all donations (PP population). The ratio of collected plasma volume over total plasma volume versus donor's total plasma volume is shown for the control and experimental groups in the PP population. Total plasma volume was calculated using the following formula: PV (cPV) = (1 − hematocrit) * Blood Volume (BV). For blood volume calculation, the following formula was used: BV = 70/√([BMI/22]). 21 Open red circles represent plasma collections in the control group, whereas open blue circles represent plasma collections in the experimental group. The yellow and green symbols represent plasma collections in the control and experimental groups that were associated with significant hypotensive AEs. The severity of the significant hypotensive AE (1.2, 1.3, 1.4, or 1.5) is denoted by symbols +, ×, ⦻, ❋, respectively. AE, adverse event; BMI, body mass index; Hyp., hypotensive; PP, per protocol; Sig., significant

FIGURE 3

Cumulative number of significant hypotensive AEs and predicted total plasma volume difference throughout the study duration. The cumulative number of significant hypotensive AEs in relation to the progression of the clinical trial is shown for the control and experimental groups. The x‐axis corresponds to the progression of the trial in weeks. The y‐axis represents the number of significant hypotensive (vasovagal/hypovolemia) AEs (shown with lines), whereas the y‐axis on the right shows the predicted difference in total plasma volume. The solid red line represents the control group, whereas the solid blue line represents the experimental group. The shaded purple area represents the difference in cumulative collected plasma volume in the experimental versus the control group. In addition, the severity of the significant hypotensive AE (1.2, 1.3, 1.4, or 1.5) is shown. AE, adverse event