Abstract

Kidney transplant recipients are at an increased risk of severe COVID-19-associated hospitalisation and death. Vaccination has been a key public health strategy to reduce disease severity and infectivity, but the effectiveness of COVID vaccines is markedly reduced in kidney transplant recipients. Urgent strategies to enhance vaccine efficacy are needed.

Methods: RIVASTIM-rapamycin is a multicentre, randomised, controlled trial examining the effect of immunosuppression modification prior to a third dose of COVID-19 vaccine in kidney transplant recipients who have failed to develop protective immunity to a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to either remain on standard of care immunosuppression with tacrolimus, mycophenolate, and prednisolone (control) or cease mycophenolate and commence sirolimus (intervention) for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm who develop protective serological neutralisation of live SARS-CoV-2 virus at 4–6 weeks following a third COVID-19 vaccination. Secondary outcomes include SARS-CoV-receptor binding domain IgG, vaccine-specific immune cell populations and responses, and the safety and tolerability of sirolimus switch.

Discussion: Immunosuppression modification strategies may improve immunological vaccine response. We hypothesise that substituting the mTOR inhibitor sirolimus for mycophenolate in a triple drug regimen will enhance humoral and cell-mediated responses to COVID vaccination for kidney transplant recipients.

Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12621001412820. Registered on 20 October 2021; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382891&isReview=true

Details

Title
Rapamycin and inulin for booster vaccine response stimulation (RIVASTIM)—rapamycin: study protocol for a randomised, controlled trial of immunosuppression modification with rapamycin to improve SARS-CoV-2 vaccine response in kidney transplant recipients
Author
Tunbridge, Matthew 1   VIAFID ORCID Logo  ; Perkins, Griffith B. 2 ; Singer, Julian 3 ; Salehi, Tania 1 ; Ying, Tracey 3 ; Grubor-Bauk, Branka 4 ; Barry, Simon 5 ; Sim, Beatrice 1 ; Hissaria, Pravin 6 ; Chadban, Steven J. 3 ; Coates, P. Toby 7 

1  The Royal Adelaide Hospital, Central and Northern Adelaide Renal and Transplantation Service (CNARTS), Adelaide, Australia (GRID:grid.416075.1) (ISNI:0000 0004 0367 1221) 
2  The University of Adelaide, School of Biological Sciences, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304); SA Pathology, Adelaide, Australia (GRID:grid.414733.6) (ISNI:0000 0001 2294 430X) 
3  Kidney Centre, Royal Prince Alfred Hospital, Department of Renal Medicine, Sydney, Australia (GRID:grid.413249.9) (ISNI:0000 0004 0385 0051); University of Sydney, Kidney Node, Charles Perkins Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
4  The University of Adelaide, Discipline of Medicine, Adelaide Medical School, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304); Basil Hetzel Institute for Translational Research, Viral Immunology Group, Adelaide, Australia (GRID:grid.488717.5) 
5  The University of Adelaide, Discipline of Medicine, Adelaide Medical School, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304); Robinson Research Institute, University of Adelaide, Molecular Immunology, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304); Women’s and Children’s Hospital, Department of Paediatric Medicine, North Adelaide, Australia (GRID:grid.1694.a) 
6  The Royal Adelaide Hospital, Department of Immunology, Adelaide, Australia (GRID:grid.416075.1) (ISNI:0000 0004 0367 1221) 
7  The Royal Adelaide Hospital, Central and Northern Adelaide Renal and Transplantation Service (CNARTS), Adelaide, Australia (GRID:grid.416075.1) (ISNI:0000 0004 0367 1221); The University of Adelaide, Discipline of Medicine, Adelaide Medical School, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304) 
Pages
780
Publication year
2022
Publication date
Dec 2022
Publisher
Springer Nature B.V.
e-ISSN
17456215
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s13063-022-06634-w
ProQuest document ID
2808568226
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.