Researchers in the Netherlands are launching a randomized clinical trial to determine whether elderly kidney transplant recipients can safely be switched to tacrolimus monotherapy, a pared-down immunosuppressive regimen that the investigators hope will reduce infection-related deaths and improve quality of life. The study, called TACMONO-XL, is a study protocol published in BMC Nephrology describing the trial’s rationale and design; it has not yet produced results on whether the approach works.
The motivation rests on a shifting demographic in transplantation. According to the protocol, 40 percent of all kidney recipients in the Netherlands are now older than 60 at the time of transplantation. Older recipients are described as more prone to infections and malignancy, and death with a functioning graft is the major cause of graft loss in this group. At the same time, the incidence of rejection and rejection-related graft loss is substantially lower in elderly recipients, which the investigators argue makes reduced immunosuppression a rational strategy for balancing rejection prevention against drug side effects.
The trial’s central hypothesis is timing-based. Because the incidence of rejection sharply decreases after the first months following transplantation, the researchers propose that reducing immunosuppressive medication after three months, leading to tacrolimus monotherapy at one year, could result in fewer infections and better patient survival in recipients aged 60 and older compared with standard immunosuppression. This remains a hypothesis to be tested; the protocol itself reports no outcome data.
TACMONO-XL is designed as an open-label, randomized, multicenter clinical trial that will enroll 306 kidney transplant recipients aged 60 years or older, randomized three months after transplantation. All participants will initially receive basiliximab induction therapy followed by maintenance treatment with tacrolimus, mycophenolate mofetil and prednisone, the standard triple immunosuppressive regimen.
Entry into the randomization is selective. The major criteria are an estimated glomerular filtration rate of at least 25 ml/min per 1.73 m2 and no prior T cell depletion or antibody-mediated rejection. Recipients who meet these criteria are then randomized to one of two paths: continuation of the triple immunosuppressive regimen, or a phased withdrawal in which prednisone is tapered between three and six months, mycophenolate mofetil is stopped thereafter, and tacrolimus alone is continued from 12 months onward.
The primary endpoints are infection-related death and infectious burden. Important secondary endpoints include graft and patient survival, rejection-free survival, and quality of life. Follow-up will continue until three years after transplantation, giving the trial a long observation window for both infectious complications and rejection events.
The design reflects a deliberate trade-off. Immunosuppressive drugs prevent the immune system from rejecting the transplanted organ, but the same suppression leaves patients vulnerable to infections and malignancies. Whether the monotherapy arm achieves that balance without triggering an unacceptable rise in rejection is precisely what the trial is built to measure.
As the protocol’s discussion states, the TACMONO-XL trial will show whether tacrolimus monotherapy as long-term maintenance therapy after kidney transplantation in the elderly results in fewer infections and infection-related death without an increase in rejection incidence while improving quality of life. That statement describes the trial’s objective, not a finding; no efficacy or safety results exist yet, and the open-label design means participants and clinicians will know which regimen is being given.
The trial is registered under EU trial number 2024-517709-10-00, registered June 6, 2025. If the hypothesized benefits are confirmed in the completed trial, the findings could reshape maintenance immunosuppression for a growing population of older transplant recipients; if rejection rates rise instead, the current standard regimen would retain its place. Either outcome would depend on the three-year follow-up data that the trial has yet to generate.
Subject of Research: A randomized trial protocol testing tacrolimus monotherapy versus standard triple immunosuppression in elderly kidney transplant recipients
Article Title: Rationale and design of the TACMONO-XL trial; a randomized trial of tacrolimus monotherapy compared to standard triple immune suppressive medication in elderly recipients of a kidney transplant to reduce infection-related mortality and improve quality of life
Article References: Betjes, M. G. H., Bemelman, F. J., Hilhorst, M. L., Litjens, N. H. R., Hesselink, D. A., van Zuilen, A. D., Berger, S. P., Geurts, F., & Sanders, J. S. F. (2026). Rationale and design of the TACMONO-XL trial; a randomized trial of tacrolimus monotherapy compared to standard triple immune suppressive medication in elderly recipients of a kidney transplant to reduce infection-related mortality and improve quality of life. BMC Nephrology. https://doi.org/10.1186/s12882-026-05494-9
Image Credits: AI Generated
DOI: 10.1186/s12882-026-05494-9
Keywords: kidney transplantation, tacrolimus monotherapy, immunosuppression, elderly recipients, TACMONO-XL, infection-related mortality, rejection, study protocol, quality of life, BMC Nephrology, clinical trial design, Rationale
News Source: Ophelia Keating. (November 4, 2026). TACMONO-XL trial to test whether tacrolimus monotherapy can cut infections in older kidney transplant recipients. Scienmag.
