Transplant Trial Watch

Association of Cytomegalovirus (CMV) DNAemia With Long-Term Mortality in a Randomized Trial of Preemptive Therapy and Antiviral Prophylaxis for Prevention of CMV Disease in High-Risk Donor Seropositive, Recipient Seronegative Liver Transplant Recipients.

Kumar, L., et al

Clinical Infectious Diseases 2024; 78(3): 719-722.

This is a post hoc study of the CAPSIL study, a randomised controlled trial that compared preemptive therapy versus antiviral prophylaxis for preventing Cytomegalovirus (CMV) disease in CMV-seronegative liver transplant patients with seropositive donors.

Participants were randomly assigned to receive either preemptive therapy or antiviral prophylaxis.

205 seronegative liver transplant recipients with seropositive donors.

The main outcomes of interest were long-term survival, CMV DNAemia and association of CMV DNAemia with mortality.

5 years post-transplant

CET Conclusions
The CAPSIL trial compared two strategies for preventing CMV disease in high-risk liver transplant patients (donor positive, recipient negative). Pre-emptive therapy (PET), where valganciclovir is only administered when CMV viraemia is detected on surveillance testing, was found to be superior to antiviral prophylaxis, where all patients are treated for 100 days post-transplant. This post-hoc analysis of CAPSIL trial data sought to determine whether this benefit in short-term outcomes resulted in long-term mortality benefit. The authors utilised a landmark survival analysis of 100 days but found no significant difference in 5-year survival. Extending the landmark to 12 months did show improved survival with PET, but as this excluded a number of patient deaths which, by chance, favoured the PET group, this cannot be taken as generalisable. The original CAPSIL trial found evidence to support the hypothesis that PET resulted in increased immunity to CMV. However, whether this results in significant improvements in overall survival was not adequately demonstrated by this post-hoc analysis.

Trial registration - NCT01552369

Funding source
Non-industry funded