Tremor outcomes after conversion from immediate-release to LCP tacrolimus in lung transplant recipients: a randomized controlled trial

Tremor is an important, dose-dependent side effect of tacrolimus in lung transplant (LTx) recipients. We assessed whether once-daily extended-release Life Cycle Pharma (LCP) tacrolimus with lower peak concentrations results in less tremor compared with twice-daily immediate-release (IR) tacrolimus. The prospective, randomized, controlled REVOLUTION trial (NCT05001074) randomized LTx recipients to either continue IR-tacrolimus or to switch to LCP-tacrolimus. Tremor was assessed with linear mixed models, objectively with the Fahn-Tolosa-Marin Tremor Rating Scale part B and subjectively with a Visual Analog Scale, at baseline and after 1 and 2 years. We included 65 LTx recipients (56.9% men; median age: 61.8 [45.0–66.6] years), with a median of 4.9 [2.1–8.1] years having passed since their transplantation. Baseline tremor severity did not differ significantly between groups (objective tremor: IR: 5.5 [3.5–8.0] vs. LCP: 6.8 [5.5–8.3]; p = 0.3 and subjective tremor: IR: 10.0 [5.0–30.0] vs. LCP: 20.0 [10.0–30.0], p = 0.1). Tremor severity remained similar between groups over time after adjusting for age, time since transplantation, tacrolimus trough levels, and kidney function. Higher age and higher tacrolimus trough levels were associated with greater objective tremor severity (β = 0.22, p = 0.001 and β = 0.21, p = 0.036, respectively). This is, to our knowledge, the first randomized clinical trial in lung transplant recipients to evaluate the effect of conversion from IR to LCP tacrolimus on tremor severity showing no effect. Clinical Trial Registration ClinicalTrials.gov , identifier NCT05001074.