None listed
Conditions
Brief summary
The RIVASTIM trials aim to identify strategies to improve immunological responses to a 3rd booster dose of the mRNA Pfizer Comirnaty COVID-19 vaccine in a cohort of kidney transplant patients who have failed to achieve an adequate immune response to a standard two-dose COVID-19 vaccine course. Kidney transplant patients are a highly vulnerable group of immunosuppressed patients who suffer from disproportionately high COVID-19-related morbidity and mortality. The transplant medication sirolimus shows promise in enhancing immune responses to COVID-19 vaccination. In this study kidney transplant patients receiving standard of care immunosuppression with tacrolimus, mycophenolate, and steroids will be randomised to either switch from mycophenolate to sirolimus, or remain on standard of care immunosuppression. Four weeks after randomisation, participants will receive a 3rd COVID-19 vaccine dose, and immunological responses will be assessed 4-6 weeks later.
Interventions
Kidney transplant recipients receiving standard of care immunosuppression with tacrolimus, mycophenolate, and steroids, who are deemed to be non-responders or low-responders to conventional 2-dose COVID-19 vaccination, will be randomised to switch from mycophenolate to sirolimus. Participants will initially have mycophenolate ceased, and sirolimus tablets commenced at 2mg daily. The dose of sirolimus will be adjusted weekly to target trough levels of 3-6 ng/mL. Once sirolimus levels are therapeu
Kidney transplant recipients receiving standard of care immunosuppression with tacrolimus, mycophenolate, and steroids, who are deemed to be non-responders or low-responders to conventional 2-dose COVID-19 vaccination, will be randomised to switch from mycophenolate to sirolimus. Participants will initially have mycophenolate ceased, and sirolimus tablets commenced at 2mg daily. The dose of sirolimus will be adjusted weekly to target trough levels of 3-6 ng/mL. Once sirolimus levels are therapeutic, tacrolimus dose will be adjusted to target trough levels of 3-5 ng/mL. Adherence will be monitored through weekly drug level monitoring. Four weeks after randomisation, participants will receive a 3rd COVID-19 mRNA vaccine dose (Pfizer Comirnaty). All participants will receive COVID vaccination during a clinical trial visit to ensure adherence. Participants will continue the altered immunosuppression regimen until measurement of vaccine responses at 4-6 weeks post vaccination. At that stage patients will be able to either continue the intervention immunosuppression or switch back to usual immunosuppression in conjunction with their treating nephrologist.
Sponsors
Professor P. Toby H Coates (MBBS FRACP PhD)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Investigator)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
- Kidney transplant recipients - Aged 18-70 years - estimated GFR >25 mL/min - Spot urinary albumin:creatinine ratio <100 mg/µmol - Current immunosuppression regimen comprising tacrolimus, mycophenolate, prednisolone - Treating nephrologist agrees that patient is suitable for sirolimus maintenance immunosuppression - Have received 2 doses of a COVID-19 vaccine regimen (either adenoviral vector or mRNA-based) and have demonstrably not responded (anti-Receptor Binding Domain antibody titre < 100 U/mL)
Exclusion criteria
- Multi-organ transplant recipients (e.g. kidney-pancreas) - Aged <18 years or >70 years - Significant kidney dysfunction, estimated GFR =25 mL/min or spot urinary albumin:creatinine ratio =100 mg/µmol - Unable or unwilling to provide informed consent to participate in the trial - Have received 2 doses of a COVID-19 vaccine regimen (either adenoviral vector or mRNA-based) and have mounted an adequate immune response (anti-Receptor Binding Domain antibodies >100 U/mL) - Have had documented infection with COVID-19 - Known allergy to or intolerance of sirolimus or everolimus - Patients who are currently pregnant
Outcome results
None listed