Viral load-guided immunosuppression after lung transplantation (VIGILung)-study protocol for a randomized controlled trial

Jens Gottlieb, Alexander Reuss, Konstantin Mayer, Karin Weide, Carmen Schade-Brittinger, Susanne Hoyer, Peter Jaksch, Jens Gottlieb, Alexander Reuss, Konstantin Mayer, Karin Weide, Carmen Schade-Brittinger, Susanne Hoyer, Peter Jaksch

Abstract

Background: Immunosuppression including high-dose calcineurin inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with a risk of graft injury. Adaptation of CNI-based immunosuppression by monitoring of torque teno virus (TTV), a latent nonpathogenic DNA virus, measured in the whole blood in addition to conventional therapeutic drug monitoring may reduce the toxicity of immunosuppression with similar efficacy.

Methods/design: An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as an add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 to 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (arm 1: immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements of renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss, and infections.

Discussion: The results of this randomized controlled trial may reduce the toxicity of immunosuppression after lung transplantation while maintaining the efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.

Trial registration: ClinicalTrials.gov NCT04198506 . Registered on 12 December 2019.

Keywords: Graft rejection; Immunosuppression; Kidney failure; Lung transplantation; Randomized controlled trial; Torque teno virus.

Conflict of interest statement

The authors declare to have no competing interests.

Figures

Fig. 1
Fig. 1
Trial flow chart and treatment groups
Fig. 2
Fig. 2
Adaptation of immunosuppression in the treatment groups
Fig. 3
Fig. 3
Data collection time points (SPIRIT figure)

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Source: PubMed

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