Table 2.
Selection criteria for FIDELIO-DKD/FIGARO-DKD [17, 18] and how they apply to the DPV/DIVE CKD population (n = 65,168)
| FIDELIO-DKD / FIGARO-DKD | Eligible DPV/DIVE patients | Ineligible DPV/DIVE patients | |
|---|---|---|---|
| Inclusion criteria | Men or women aged 18 years and older | Identical | Identical |
| Women of child-bearing potential with a negative pregnancy test and agreeing to use adequate contraception | Not available | Not available | |
| Patients with T2DM as defined by the American Diabetes Association | Identical | Identical | |
| Patients with a clinical diagnosis of CKD (see Table 1) | Identical | Identical | |
| Prior treatment with ACEIs or ARBs | Identical | Excluded | |
| Serum potassium ≤ 4.8 mmol/L at both the run-in and screening visits | Identical | Excluded | |
| Exclusion criteria | |||
| Medical and surgical history | Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis | Excluded (based on Analgesic nephropathy, IgA nephropathy, Lithium, Lupus nephritis, xanthine oxidase deficiency, chemotherapy toxicity) | Included |
| UACR > 5,000 mg/g (> 565 mg/mmol) at the run-in or screening visit | Excludeda (based on the median of the last year) | Included | |
| Glycosylated hemoglobin > 12% (> 108 mmol/mol) at the run-in or screening visit | Excludeda (based on the median of the last year) | Included | |
| Uncontrolled arterial hypertension with mean sitting SBP ≥ 170 mmHg or mean sitting DBP ≥ 110 mmHg at the run-in visit or mean sitting SBP ≥ 160 mmHg or mean sitting DBP ≥ 100 mmHg at the screening visit | Excludeda (based on the median of the last year) | Included | |
| SBP < 90 mmHg at the run-in or screening visit | Excludeda (based on the median of the last year) | Included | |
| Patients with a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (New York Heart Association class II–IV) at the run–in visit | Excluded: Patients with a clinical diagnosis of chronic heart failure (no discrimination between reduced and preserved EF) | Included | |
| Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for worsening heart failure, in the 30 days before the screening visit | Excluded | Included | |
| Dialysis for acute renal failure in the 12 weeks before the run-in visit | Excluded | Included | |
| Renal allograft in place or a scheduled kidney transplant in the 12 months after the run-in visit | Excluded | Included | |
| Addison’s disease | Excluded | Included | |
| Hepatic insufficiency classified as Child–Pugh C | Excluded | Included | |
| Medication and drug use | Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic which cannot be discontinued at least 4 weeks before the screening visit | Excluded: Potassium sparing: Amiloride, Triamterene, spironolactone and eplerenone | Included |
| Concomitant therapy with both ACEIs and ARBs which cannot be discontinued for the purpose of the studies | No information on the ability to discontinue ACEi/ARB | Included | |
| Concomitant therapy with potent cytochrome P450 isoenzyme 3A4 inhibitors or inducers (to be stopped at least 7 days before randomization) | Excluded | Included | |
| Other | Any other condition or therapy which would make the patient unsuitable for the studies and would not allow participation for the full planned study period (e.g., active malignancy or other condition limiting life expectancy to < 12 months) | Excluded: Active malignancy or other condition limiting life expectancy to < 12 months | Included |
| Pregnant or breast-feeding or intention to become pregnant during the studies | Not available | Included | |
| Not applicable | Written, informed consent signed before any study-specific procedure | Not applicable | Not applicable |
| Known hypersensitivity to study tx (active substance or excipients) | Not applicable | Not applicable | |
| Previous assignment to treatment during the studies | Not applicable | Not applicable | |
| Previous (within 30 days before randomization) or concomitant participation in another clinical study (i.e., Phase I–III clinical studies) with investigational medicinal product, except for participation in the run-in and screening periods of Studies 17,530 and 16,244 | Not applicable | Not applicable | |
| Close affiliation with the investigational site: for example, a close relative of the investigator or dependent person (e.g., employee or student of the investigational site) | Not applicable | Not applicable |
ACEI angiotensin-converting enzyme inhibitor; ARB angiotensin receptor blocker; CKD-EPI Chronic Kidney Disease Epidemiology Collaboration; DBP diastolic blood pressure; DKD diabetic kidney disease; eGFR estimated glomerular filtration rate; EF ejection fraction; SBP systolic blood pressure; T2DM type 2 diabetes mellitus; UACR urinary albumin-to-creatinine ratio
aThere is no run-in or screening visit in DPV/DIVE so it was assumed to be equivalent to the last visit (cross-section)