Table 2 Primary and secondary endpoints of the OPTIMIZE study

Primary endpoint

‘successful transplantation’

At 24 months after transplantation: survival with a functioning allograft with an estimated GFR above 30 (stratum A) or 45 (stratum B) ml/min per 1.73 m².

Main secondary endpoint

Primary objective, analyzed separately per stratum

-

Other secondary endpoints

Incidence of individual endpoints of death, graft loss, eGFR below 30 or 45 ml/min/1.73m²

At 12 and 24 months after transplantation

Evolution of renal function over time by slope analysis

eGFR and creatinine clearance, based on the 24 hour excretion of creatinine in the urine

Incidence of treated biopsy-proven rejection (tBPAR)

Will be checked and recorded at every study visit

Rejection treatment and type of rejection treatment

Will be checked and recorded at every study visit

Development of donor-specific anti-HLA antibodies

At 12 and 24 months after transplantation: DSA as measured by Luminex

Incidence of (drug-related)adverse events, serious adverse events and adverse reactions, including drug-related discontinuation of study medication

All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded

Incidence of clinically relevant infections, post transplantation diabetes mellitus, malignancies and cardiovascular events

All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded

Presence of frailty after transplantation and change in frailty from baseline

At baseline: clinical frailty score and hand grip strength.

At 12 and 24 months after transplantation: clinical frailty score, hand grip strength, Fried Frailty Index

Physical and cognitive functioning and changes over time

At 12 and 24 months after transplantation: Short Physical Performance Battery, Montreal Cognitive Assessment

Health-related quality of life at 0, 12 and 24 months and changes from baseline

Questionnaires: Short-Form-12 and European Quality of life-5 Dimensions

Difference in illness perception at 0, 12 and 24 months and changes from baseline

Questionnaire: Brief Illness Perception Questionnaire

Difference in symptoms at 0, 12 and 24 months and changes from baseline

Questionnaire: Dialysis Symptom Index with additional items from the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59

Difference in adherence of immunosuppressive medication at 12 and 24 months

Questionnaire: Basel Assessment of Adherence to Immunosuppressive Medication Scale

Presence of markers for immunosenescence at 12 and 24 months and changes from baseline

T cell differentiation, exhaustion and telomere length will be assessed by flowcytometry of Peripheral Blood Mononuclear Cells

Difference in iBOX predicted outcome at 3, 5 and 7 years

Based on the available data

Development of a pharmacokinetic model for tacrolimus once-daily (Envarsus®), using data on AUC’s

In addition to trough levels, additional AUC’s will be withdrawn at the Leiden University Medical Center as routine patient care on week 2 and 6.

Other

Evaluation of Cost-effectiveness of the new immunosuppressive regimen, and comparison to the current standard of care

Cost-effectiveness of the immunosuppressive regimen will be evaluated using state-of-the-art health-economic techniques; costs and effectiveness of immunosuppressive therapy will be derived from the study