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
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 recip...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-022-06634-w |
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| author | Matthew Tunbridge Griffith B. Perkins Julian Singer Tania Salehi Tracey Ying Branka Grubor-Bauk Simon Barry Beatrice Sim Pravin Hissaria Steven J. Chadban P. Toby Coates |
| author_facet | Matthew Tunbridge Griffith B. Perkins Julian Singer Tania Salehi Tracey Ying Branka Grubor-Bauk Simon Barry Beatrice Sim Pravin Hissaria Steven J. Chadban P. Toby Coates |
| author_sort | Matthew Tunbridge |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-04-12T21:07:13Z |
| format | Article |
| id | doaj.art-68bb6692f70f450b8db0d139ac85c8fc |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-12T21:07:13Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-68bb6692f70f450b8db0d139ac85c8fc2022-12-22T03:16:41ZengBMCTrials1745-62152022-09-0123111210.1186/s13063-022-06634-wRapamycin 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 recipientsMatthew Tunbridge0Griffith B. Perkins1Julian Singer2Tania Salehi3Tracey Ying4Branka Grubor-Bauk5Simon Barry6Beatrice Sim7Pravin Hissaria8Steven J. Chadban9P. Toby Coates10Central and Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide HospitalSchool of Biological Sciences, The University of AdelaideDepartment of Renal Medicine, Kidney Centre, Royal Prince Alfred HospitalCentral and Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide HospitalDepartment of Renal Medicine, Kidney Centre, Royal Prince Alfred HospitalDiscipline of Medicine, Adelaide Medical School, The University of AdelaideDiscipline of Medicine, Adelaide Medical School, The University of AdelaideCentral and Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide HospitalDepartment of Immunology, The Royal Adelaide HospitalDepartment of Renal Medicine, Kidney Centre, Royal Prince Alfred HospitalCentral and Northern Adelaide Renal and Transplantation Service (CNARTS), The Royal Adelaide HospitalAbstract 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=truehttps://doi.org/10.1186/s13063-022-06634-wKidney transplantationRandomised controlled trialSirolimusImmunosuppressionSARS-CoV-2COVID-19 |
| spellingShingle | Matthew Tunbridge Griffith B. Perkins Julian Singer Tania Salehi Tracey Ying Branka Grubor-Bauk Simon Barry Beatrice Sim Pravin Hissaria Steven J. Chadban P. Toby Coates 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 Trials Kidney transplantation Randomised controlled trial Sirolimus Immunosuppression SARS-CoV-2 COVID-19 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Kidney transplantation Randomised controlled trial Sirolimus Immunosuppression SARS-CoV-2 COVID-19 |
| url | https://doi.org/10.1186/s13063-022-06634-w |
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