Table 1 Study endpoints
Description | Specific measurement variable | |
|---|---|---|
Primary outcome | ||
Proportion of patients with CMV reactivation | Quantification of viral DNA copies in blood and urine by quantitative polymerase chain reaction (qPCR) | |
Secondary outcomes | ||
Safety | Number of adverse events and incidence of events by system organ class | |
Adverse events sufficient to stop treatment with study drug | ||
Change in the proportion of CD4 + CD28null cells from baseline to 6 months | Proportion of CD3 + CD4 + CD28- T cells in peripheral blood | |
Change in the concentration of soluble markers of inflammation from baseline to 6 months | Concentration of IL-2, tumour necrosis factor alpha (TNF-α), IFN-γ, IL-6, IL-10, IL-17 and highly sensitive C-reactive protein (CRP) in peripheral blood | |
Tertiary outcome | ||
Persistence of valaciclovir effect on the proportion of CD4 + CD28null cells from 6 months to 12 months | Proportion of CD3 + CD4 + CD28- T cells in peripheral blood | |
Exploratory outcomes | ||
Change in immune phenotype of CD4+ T cells from baseline to 6 months | Proportion of CD4 + CD28null cells secreting IFN-γ, IL-2, TNF-α, IL-5 and IL-10 in response to CMV lysate stimulation | |
Proportion of CD4 + CD28null cells expressing the inhibitory receptors PD-1, TIM-3, CTLA-4 and lymphocyte activation gene 3 (LAG-3) | ||
Proportion of CD4 + CD28null cells expressing the transcription factors T box expressed in T cells (T-bet) and positive regulatory (PR) domain zinc finger protein 1 (BLIMP-1) | ||
Proportion of CD4 + CD28null cells expressing the chemokine receptors CX3CR1, CXCR3, C-C chemokine receptor type 5 (CCR5), CD49d and CD11b | ||
Proportion of CD4+ naive, central memory, effector memory and terminally differentiated effector memory populations | ||
Change in soluble markers of endothelial damage from baseline to 6 months | Concentration of fractalkine, IP-10, regulated on activation, normal T cell expressed and secreted (RANTES), P-selectin, E-selectin, monocyte chemoattractant protein-1 (MCP-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble intracellular cell adhesion molecule 1 (sICAM-1) in peripheral blood | |
Change in markers of arterial stiffness from baseline to 6 months | Measures of arterial stiffness: cfPWV, peripheral pulse pressure and central pulse pressure |