TY - JOUR
T1 - Hypersensitivity incidence after sugammadex administration in healthy subjects
T2 - a randomised controlled trial
AU - Min, K. C.
AU - Bondiskey, P.
AU - Schulz, V.
AU - Woo, T.
AU - Assaid, C.
AU - Yu, W.
AU - Reynders, T.
AU - Declercq, R.
AU - McCrea, J.
AU - Dennie, J.
AU - Adkinson, F.
AU - Shepherd, G.
AU - Gutstein, D. E.
N1 - Funding Information:
The authors would like to acknowledge the principal investigators in this study: Luc Van Bortel, Magdalena Petkova, Dennis Swearingen, Martha Hernandez-Illas, George J. Atiee, Sophia Young, Elizabeth Richardson, Marco Ordonez, Richard Kessler, and Gary Lamunion for their assistance in monitoring the study. The authors also thank the healthy volunteers who participated in this study. The authors would also like to thank the medical writing support, including assisting authors with the development of the draft, which was provided by Melanie More, BSc; the incorporation of comments by Camille Bonomelli, PhD; and editorial support, including figure preparation, formatting, and submission, which was provided by Sinead Stewart (all of Scion, London, UK). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and data checking of information provided in the manuscript. However, the ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors.
Funding Information:
The authors would like to acknowledge the principal investigators in this study: Luc Van Bortel, Magdalena Petkova, Dennis Swearingen, Martha Hernandez-Illas, George J. Atiee, Sophia Young, Elizabeth Richardson, Marco Ordonez, Richard Kessler, and Gary Lamunion for their assistance in monitoring the study. The authors also thank the healthy volunteers who participated in this study. The authors would also like to thank the medical writing support, including assisting authors with the development of the draft, which was provided by Melanie More, BSc; the incorporation of comments by Camille Bonomelli, PhD; and editorial support, including figure preparation, formatting, and submission, which was provided by Sinead Stewart (all of Scion, London, UK). This assistance was funded by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc. , Kenilworth, NJ, USA. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and data checking of information provided in the manuscript. However, the ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors.
Publisher Copyright:
© 2018 British Journal of Anaesthesia
PY - 2018/10
Y1 - 2018/10
N2 - Background: We evaluated the incidence of hypersensitivity or anaphylaxis after repeated single-dose sugammadex administration in non-anaesthetised adults. Methods: In this multicentre, double-blind study (NCT02028065), healthy volunteer subjects were randomised (2:2:1 ratio) to one of three groups to receive three repeated intravenous injections of sugammadex 4 or 16 mg kg−1, or placebo, separated by a ∼5 week intervals. Targeted hypersensitivity assessments were performed 0.5, 4, and 24 h post-dosing, and hypersensitivity signs/symptoms were referred to a blinded independent Adjudication Committee. Anaphylaxis was determined per Sampson (Criterion 1). The primary endpoint was the proportion with confirmed hypersensitivity. Results: Of 375 evaluable subjects, 25 had confirmed hypersensitivity [sugammadex 4 mg kg−1: 10/151 (6.6%); sugammadex 16 mg kg−1: 14/148 (9.5%); placebo: 1/76 (1.3%)]. The differences in incidence rates vs placebo were 5.3% (95% confidence interval: –0.9, 10.7) for sugammadex 4 mg kg−1 and 8.1% (1.7, 14.2) for 16 mg kg−1. Incidence was similar across sugammadex doses and dosing occasions, including in subjects with reactions to previous doses. Three subjects (16 mg kg−1 group) required antihistamines/corticosteroids and discontinued the study, per protocol; symptoms resolved and no subject required epinephrine. One subject with anaphylaxis after the first 16 mg kg−1 dose recovered completely post-treatment. There were no clinically relevant anti-sugammadex antibody or tryptase findings. Conclusions: Hypersensitivity in response to sugammadex administration can occur in healthy subjects without history of previous sugammadex exposure. Hypersensitivity incidence was similar across sugammadex doses and numerically higher than placebo, with no evidence of sensitisation with repeated administration. Hypersensitivity is unlikely to be mediated through sugammadex-specific immunoglobulin G- or E-mediated mast cell stimulation in healthy volunteers. Clinical trial registration: NCT02028065.
AB - Background: We evaluated the incidence of hypersensitivity or anaphylaxis after repeated single-dose sugammadex administration in non-anaesthetised adults. Methods: In this multicentre, double-blind study (NCT02028065), healthy volunteer subjects were randomised (2:2:1 ratio) to one of three groups to receive three repeated intravenous injections of sugammadex 4 or 16 mg kg−1, or placebo, separated by a ∼5 week intervals. Targeted hypersensitivity assessments were performed 0.5, 4, and 24 h post-dosing, and hypersensitivity signs/symptoms were referred to a blinded independent Adjudication Committee. Anaphylaxis was determined per Sampson (Criterion 1). The primary endpoint was the proportion with confirmed hypersensitivity. Results: Of 375 evaluable subjects, 25 had confirmed hypersensitivity [sugammadex 4 mg kg−1: 10/151 (6.6%); sugammadex 16 mg kg−1: 14/148 (9.5%); placebo: 1/76 (1.3%)]. The differences in incidence rates vs placebo were 5.3% (95% confidence interval: –0.9, 10.7) for sugammadex 4 mg kg−1 and 8.1% (1.7, 14.2) for 16 mg kg−1. Incidence was similar across sugammadex doses and dosing occasions, including in subjects with reactions to previous doses. Three subjects (16 mg kg−1 group) required antihistamines/corticosteroids and discontinued the study, per protocol; symptoms resolved and no subject required epinephrine. One subject with anaphylaxis after the first 16 mg kg−1 dose recovered completely post-treatment. There were no clinically relevant anti-sugammadex antibody or tryptase findings. Conclusions: Hypersensitivity in response to sugammadex administration can occur in healthy subjects without history of previous sugammadex exposure. Hypersensitivity incidence was similar across sugammadex doses and numerically higher than placebo, with no evidence of sensitisation with repeated administration. Hypersensitivity is unlikely to be mediated through sugammadex-specific immunoglobulin G- or E-mediated mast cell stimulation in healthy volunteers. Clinical trial registration: NCT02028065.
KW - anaphylaxis
KW - hypersensitivity
KW - neuromuscular block
KW - sugammadex
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U2 - 10.1016/j.bja.2018.05.056
DO - 10.1016/j.bja.2018.05.056
M3 - Article
C2 - 30236237
AN - SCOPUS:85052097485
SN - 0007-0912
VL - 121
SP - 749
EP - 757
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 4
ER -