Combined low-dose everolimus and low-dose tacrolimus after Alemtuzumab induction therapy: a randomized prospective trial in lung transplantation.Benazzo, A., et al.
Trials [Electronic Resource] 2021; 22(1): 6.
The aim of this protocol is to determine the effect of combining low-dose tacrolimus and low-dose everolimus following alemtuzumab induction therapy in lung transplant patients.
Participants will be randomised to two groups: the treatment group, where patients will receive the new maintenance immunosuppression protocol with low-dose everolimus and low-dose tacrolimus; and the control group, in which patients will receive the standard immunosuppression protocol.
Adult lung transplant patients.
The primary outcome is the measurement of estimated glomerular filtration rate (eGFR). The secondary outcomes include the incidence of acute cellular rejection, chronic lung allograft dysfunction, antibody-mediated rejection, lymphocytic bronchiolitis, de novo donor-specific antibodies (dnDSA), and survival.
This is the study protocol for an RCT in lung transplantation. The hypothesis is that, following induction with Alemtuzumab, maintenance immune suppression with a two-drug regimen consisting of low-dose everolimus and tacrolimus can improve kidney function. There are a number of good quality indicators in this protocol. 110 patients will be randomised to one of two study arms. Randomisation will be by centralised computer system, and it will not be possible to determine in advance to which arm they will be assigned (allocation concealment). However, there will be a degree of stratification to make sure that similar numbers of patients with high risk conditions are spread between the arms (CMV status and eGFR ranges). This will not impact on the allocation concealment aspect. I agree that it would be difficult to blind the study due to the requirement for drug dose monitoring and dose adjustment. Double-checking of data entry and external monitoring is planned. The primary end-point is change in eGFR and the study is powered for this. The sample size at first glance seems small (only 55 per arm). The sample size calculation was based upon a previous study of 231 patients treated in this centre with the control regimen. Previous monitoring has suggested that eGFR falls at first and stabilises by 12 months, at median 60mL/min. The authors speculate that with the new regimen eGFR will stabilise at 72ml/min, but it is not clear what this is based upon. It may be that a smaller improvement would be clinically significant, but the study would have to increase in size significantly to see a smaller effect. The authors have made allowance for a 20% dropout rate, which is good planning. Overall the protocol is well written and describes the conduct, oversight and monitoring in detail.
EudraCT - 2018-001680-24