Table 2:
FLOW trial endpoints.
| Study endpoints | Time frame |
|---|---|
| Primary endpoint | |
| Time to first occurrence of a composite endpoint consisting of • Onset of kidney failure, defined as initiation of chronic kidney replacement therapy (dialysis or kidney transplantation) or persistent eGFR <15 ml/min/1.73 m2 for at least 4 weeks • Death from kidney failure • CV death • Onset of persistent ≥50% reduction in eGFR (CKD-EPI) versus baseline |
Randomisation to EOT |
| Confirmatory secondary endpoints | |
| Annual rate of change in eGFR (CKD-EPI) (total eGFR slope) | Randomisation to EOT |
| Time to first occurrence of a composite CV MACE endpoint consisting
of: • Non-fatal myocardial infarction • Non-fatal stroke • CV death |
Randomisation to EOT |
| Time to occurrence of all-cause death | Randomisation to EOT |
| Supportive secondary endpoints | |
| Time to occurrence of each of the individual components of the primary
composite endpoint and of the confirmatory secondary MACE endpoint |
Randomisation to EOT |
| Time to first occurrence of MALE, a composite endpoint consisting of: • Acute limb ischaemia hospitalisation • Chronic limb ischaemia hospitalisation |
Randomisation to EOT |
| Annual rate of change in eGFR (CKD-EPI) (chronic eGFR slope) | Week 12 to EOT |
| Change in eGFR (CKD-EPI) | Randomisation to week 12 |
| Change in eGFR (cystatin C CKD-EPI) | Randomisation to year 3 |
| Relative change in UACR | Randomisation to year 3 |
| Change in body weight | Randomisation to year 3 |
| Change in HbA1c | Randomisation to year 3 |
| Change in systolic blood pressure | Randomisation to year 3 |
| Change in diastolic blood pressure | Randomisation to year 3 |
| Number of severe hypoglycaemic episodes | Randomisation to EOT |
| Exploratory endpoints | |
| Change in EQ-5D-5L index score | Randomisation to year 3 |
| Change in EQ-5D-5L visual analogue scale score | Randomisation to year 3 |
Randomisation = week 0; end of trial = a period expected to be ≥61 months for the individual participant; persistent = two consecutive central laboratory assessments that meet criteria, at least 4 weeks apart. Events including deaths, those leading to kidney replacement therapy, acute coronary syndrome, stroke or transient ischaemic attack, and MALE are reviewed by an independent external EAC in a blinded manner.
EOT, end of trial; EQ-5D-5L, EuroQol five-dimension, five-level questionnaire; MALE, major adverse limb events.