Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study)

Göran Dellgren, Thomas Kromann Lund, Peter Raivio, Inga Leuckfeld, Johan Svahn, Jesper Magnusson, Gerdt C Riise, Göran Dellgren, Thomas Kromann Lund, Peter Raivio, Inga Leuckfeld, Johan Svahn, Jesper Magnusson, Gerdt C Riise

Abstract

Background: A low level of evidence exists regarding the choice of calcineurin inhibitor (CNI) for immunosuppression after lung transplantation (LTx). Therefore, we designed a randomized clinical trial according to good clinical practice rules to compare tacrolimus with cyclosporine after LTx.

Methods: The ScanCLAD study is an investigator-initiated, pragmatic, controlled, randomized, open-label, multicenter study evaluating if an immunosuppressive protocol based on anti-thymocyte globulin (ATG) induction, once-daily tacrolimus dose, mycophenolate mofetil, and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after LTx, compared to a cyclosporine-based protocol with all other immunosuppressive and prophylactic drugs being identical between groups. All patients will be followed for 3 years to determine the main endpoint of CLAD. The study is designed for superiority, and power calculations show that 242 patients are needed. Also, the study is designed with more than 10 substudies addressing other important and unresolved issues in LTx. In addition, the ScanCLAD study enabled the synchronization of the treatment and follow-up protocols of the lung transplantation programs of all five Scandinavian lung transplantation centers.

Planned outcomes: Recruitment started in 2016. At the end of April 2019, 227 patients were randomized. We anticipate the last patient to be randomized in autumn 2019, and thus the last patient visits will be in 2022. The ScanCLAD study is enrolling and investigates which CNI is to be preferred from a CLAD perspective after LTx.

Trial registry number: ScanCLAD trial registered at ClinicalTrials.gov before patient enrollment (NCT02936505). EUDRACT number 2015-004137-27.

Keywords: Calcineurin inhibitor; Chronic lung allograft dysfunction; Lung transplantation; Randomized clinical trial.

Figures

Fig. 1
Fig. 1
Design of the ScanCLAD study. LTx lung transplantation, CNI calcineurin inhibitor, CyA cyclosporine, BID twice daily, MMF mycophenolate mofetil, CS corticosteroids, Tac tacrolimus, OD once daily
Fig. 2
Fig. 2
Randomized patients at the end of April 2019 and stratified by center in the ScanCLAD study. GOT = Gothenburg, Sweden; Lund = Lund, Sweden; CPH = Copenhagen, Denmark; HELS = Helsinki, Finland; and OSLO = Oslo, Norway

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