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Table 1 Study endpoints

From: Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS): study protocol for a randomised controlled trial

  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