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. 2022 Sep 15;23(1):780.
doi: 10.1186/s13063-022-06634-w.

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

Matthew Tunbridge #  1 , Griffith B Perkins #  2   3 , Julian Singer #  4   5 , Tania Salehi  6 , Tracey Ying  4   5 , Branka Grubor-Bauk  7   8 , Simon Barry  7   9   10 , Beatrice Sim  6 , Pravin Hissaria  11 , Steven J Chadban #  4   5 , P Toby Coates #  6   7
Affiliations

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

Matthew Tunbridge et al. Trials. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Outline of the trial
Fig. 2
Fig. 2
Participant timeline. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. Enrolment, interventions, and assessments. GSRS, gastrointestinal symptom rating scale; EQ-5D, EuroQol five dimensions questionnaire; AE, adverse events; SAE, serious adverse events
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