Infectious events as primary and secondary endpoints
diarrhoea, respiratory or gastrointestinal infection, CMV infection, CMV viremia, CMV syndrome, infection, cutaneous disease
INFECTIOUS DISEASES, RESPIRATORY INFECTIONS, GRAFT LOSS, SARS-COV-2 INFECTION, URINARY TRACT INFECTIONS, VIRUS INFECTION, MINOR, INFECTIOUS DISEASE, CMV INFECTION, CMV VIREMIA, INFECTION, SECONDARY, EVENTS, VIRAL RESPIRATORY INFECTION
The primary endpoint is designed to detect consequences of too-intense immunosuppression that might be reduced by personalised TTV-guided immunosuppression. Infectious disease events are scored by assessors blinded to the allocation sequence. Diagnosis is based on the Infectious Diseases Guidelines 2019 published by the American Society according to the data provided in the eCRF. Assessors have the possibility to post queries to the investigator in case of missing information. Investigators are advised to not unblind investigators within their correspondence. Any insignificant treatment, e.g. topical antifungal treatment of minor localised cutaneous disease, or supportive treatment during viral respiratory infections, e.g. antiseptic lozenge, is excluded. Non-indicated therapy, e.g. antibiotic treatment in viral respiratory or gastrointestinal infection, is excluded. Increase of prophylactic treatment dose, e.g. in CMV syndrome, is included.SARS-CoV-2 infection with or without COVID-19 is excluded. SARS-CoV-2-positive test results still have a high incidence, with only minor differences between healthy subjects and recipients of a kidney transplant. Thus, it is unlikely that TTV-guided immunosuppression will alter the rate of infection and likely that many trial subjects in both the active and the control group will hit the primary endpoint due to COVID-19, potentially substantially reducing the power to discriminate the effect of TTV-guided immunosuppression. A high rate of COVID-19 in both groups would likely lead to non-inferiority of TTV-guided immunosuppression, but the safety of TTV-guided immunosuppression would still be unknown, rendering the trial futile.Episodes of infection scored by the treating medical personnel according to the primary endpoint are the main secondary outcome. In the routine care of kidney transplant recipients, the diagnosis and treatment of infection and graft rejection sometimes do not follow current guidelines. However, such assessments might outperform guideline-directed management in some cases. Thus, this endpoint might reflect the true rate of clinically significant infection and graft loss more accurately. However, due to the fact that investigators are not blinded towards the treatment allocation, this endpoint has a risk of assessment bias and cannot be used as primary endpoint.Infectious disease workup will be performed according to local standards. However, the investigators are asked to perform a standardised workup. For the expected main infectious events, the following parameters are of special interest: (a) for urinary tract infections, results on urinary dip stick and cultures and imaging; (b) for respiratory infections, results on imaging, microbiological and virologic workup including light microscopy, cultures, cytokine release assays, antigen tests and PCRs from blood, urine and respiratory material, albumin, respiratory rate, heart rate, peripheral oxygen saturation, arterial Ph and neurological status; (c) for diarrhoea, results on imaging and microbiological and virologic workup including cultures, antigen tests and PCRs; (d) for polyma virus infection, results on blood and urine PCR, decoy cells and kidney graft biopsy results and (e) for CMV infection differential blood count, liver enzymes (to differentiate CMV viremia from CMV syndrome), results on imaging and PCRs from liquor, urine, blood, stole and respiratory material.