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.
Keywords: COVID-19; Immunosuppression; Kidney transplantation; Randomised controlled trial; SARS-CoV-2; Sirolimus; Vaccination.
【저자키워드】 COVID-19, SARS-CoV-2, randomised controlled trial, Immunosuppression, vaccination., Kidney transplantation, Sirolimus, 【초록키워드】 public health, IgG, Efficacy, Vaccine, COVID-19 vaccine, vaccination, Trial, randomised, disease severity, Intervention, outcome, virus, COVID, COVID-19 vaccination, protective immunity, vaccine response, clinical, Effectiveness, Controlled trial, death, multicentre, registry, serological, hospitalisation, neutralisation, Protective, kidney transplant recipient, kidney transplant recipients, dose, humoral, Prednisolone, regimen, cell-mediated response, Standard of care, Tolerability, Primary outcome, increased risk, participant, live SARS-CoV-2, binding domain, Modification, recipient, mTOR inhibitor, responses, immunological, secondary, ENhance, IMPROVE, develop, include, proportion, reduced, reduce, New, 1:1, hypothesise, immune cell population, 【제목키워드】 Study protocol, randomised, SARS-CoV-2 vaccine, Rapamycin, Controlled trial, kidney transplant recipient, Booster vaccine, Modification, IMPROVE,