Plans for the assessment and collection of outcomes {18a}
abdominal pain/cramps, fever, palpitation, chills, urinary urgency/frequency, shortness of breath, abdominal pain, toxicity, tremor, infections, insomnia, tumour, diabetes, asthenia, fatigue, chest pain, pollakisuria, cough, infection, Hepatitis B, nausea, vomiting, diarrhoea, adventitious breath, Tumour, ®, psychiatric illness, paresthesia, purulent, constipation, pain, Epstein-Barr virus, dysuria, sweats, headache, flank/allograft pain, oedema
TUMOUR, PARESTHESIA, INFECTIOUS DISEASE, INFECTIONS, RESPIRATORY INFECTION, DISEASE, EVENTS, RENAL DISEASE, INFECTION, TUMOUR, CONCOMITANT DISEASE, URINARY TRACT INFECTION, HEPATITIS B, DISEASES, INFLUENZA, OEDEMA, DIABETES
Data relevant to the trial protocol are documented in the eCRF specially created for this trial (MACRO 4.0; Ennov, Paris, France). The data are checked for completeness, plausibility and consistency by means of programmed checks directly in the eCRF and by additional manual checks outside the eCRF. The data collection forms can be found in the The following data will be obtained:A detailed medical history including relevant baseline and FUP data until randomisation will be obtained. The following data will be noted: current medication, SARS-CoV-2 and influenza vaccination status, recipient sex, ethnicity and date of birth, type of renal disease, history of renal replacement therapy, history of prior transplantation, history of diabetes, history of major cardiovascular, immunological and oncological diseases and diseases currently requiring concomitant medication, CMV/ Epstein-Barr virus (EBV) serology, Hepatitis B and C serology, transplant date, donor type/age/sex, donor CMV/EBV serology, donor and recipient HLA (ideally 4-digit typing, but sufficient to define DSA), HLA mismatch, CMV/A urinary dip β-HCG-based test will be performed. All immunosuppressive and antimicrobial prophylactic medication, medication for concomitant disease and medications for the treatment of AEs and the endpoint will be noted, including name, dose and schedule. All vaccinations will be noted. To detect TAC-related AEs and toxicity, complete blood count, blood chemistry and venous blood gas analyses will be performed according to routine clinical care. In addition, neuropsychiatric, sensorial, cardiovascular, bronchial, gastrointestinal, dermatological, musculoskeletal and urogenital alterations will be noted; specifically, any nausea, vomiting, constipation, diarrhoea, abdominal pain, tremor, paresthesia, headache, mental status change, and changes in motor and sensory functions, insomnia, asthenia, pain, oedema, shortness of breath, chest pain and palpitation will be assessed. AEs will also be assessed using patient diaries.All infections have to be documented as AEs. In general, quality, onset and duration of symptoms, details on diagnostics, treatment and inpatient stay, and response to treatment have to be noted. Signs of infections that have to be documented as an AE include pain, night sweat, fever, chills, malaise, fatigue, diarrhoea (frequency and consistency of the stool), abdominal pain/cramps, dysuria, pollakisuria, alguria, urinary urgency/frequency, suprapubic pain, flank/allograft pain (on palpitation), cough, sputum (purulent, with blood), adventitious breath sounds on auscultation/palpation, shortness of breath and rapid/shallow breathing. Infectious disease workup will be performed according to local standards. However, some diagnostic workup should be performed to obtain comparable findings. In case of suspected infection, the investigators should perform a minimum diagnostic set including complete blood count, C-reactive protein, blood pressure, heart rate, respiratory rate and body temperature and document any altered mental status.In addition, the following diagnostic sets should be applied:In patients with fever: blood and urine cultures, urinary dipstick and CMV PCR from the blood.In patients with suspected urinary tract infection: urinary dipstick and urine cultures; if available, ultrasound of the urinary track system.In patients with suspected respiratory infection: chest X-ray; if available, In patients with suspected diarrhoea: stool cultures and CMV PCR from stool samples; if available, multiplex PCR from stool samples.In general, all performed supporting diagnostic tests related to infections should be documented.In addition to the trial visits, patients will be contacted at 2-week intervals via phone by the trial team, which will ask about episodes of infection (duration and onset of symptoms, diagnosis, treatment, and inpatient stay) and signs of infection (pain, fever, night sweats, cough, dysuria and diarrhoea).Indication biopsies will be evaluated by applying standard centre methodology (including HE, PAS, Trichrome, S/AFOG, silver stain and immunohistochemistry). For protocol biopsies at month 12, an additional molecular evaluation will be performed by the Molecular Microscope Diagnostic System (MMDx) at the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta, Edmonton, AB, Canada).TTV will be quantified in peripheral blood EDTA plasma using the TTV R-GENE® (bioMérieux). bioMérieux has set up TTV R-GENE® at all participating sites with a customised quality assessment programme Quality Control for Molecular Diagnostics (QCMD; UK).Tacrolimus trough level will be quantified according to the local centre standard.If not part of the routine post-transplant care, DSA monitoring on the basis of a single fluorescence bead assay has to be done.Tumour screening will be performed, not as part of the study protocol but according to local centre standards. Any oncological disease will be documented (type of tumour and date of diagnosis). Laboratory workup and virology screening will be performed according to local centre standards. However, according to the study protocol, at least leucocyte count, creatinine and urinary protein- and albumin-to-creatinine ratio will have to be assessed. Findings concerning CMV and BKV screening, including CMV and BKV PCR performed routinely at the centres, will be noted. For the assessment of health-related quality of life, the Medical Outcomes Study Short Form 36 and the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59 Items Revised will be used. A questionnaire including sociological status, education, employment, addictions, critical life events and history of psychiatric illness will be administered. Diaries will be filled by the patients, including TAC intake and occurrence of AEs. Data collection forms can be found in the 