EARLIER – an observational study to evaluate the use of cinacalcet in incident hemodialysis patients with secondary hyperparathyroidism in daily clinical practice

EARLIER – Beobachtungsstudie zur Evaluierung der Verwendung von Cinacalcet bei inzidenten Hämodialysepatienten mit sekundärem Hyperparathyreoidismus in der klinischen Praxis

SUPPLEMENTARY MATERIAL

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Sensitivity analysis estimating the impact of missing data

Table S1. Baseline Characteristics for FAS, EAS, and CAS

CAS complete analysis set; EAS evaluable analysis set; FAS full analysis set; iPTH intact parathyroid hormone

*The mean is based on n=113 patients with available iPTH values at baseline, the percentages are based on n=146 patients including those with missing iPTH values. **The number of corrected calcium values exceeds the number of albumin values in a very few instances, because corrected Ca was reported on the CRF

FAS / EAS / CAS
Parameter / N / Median (IQR) or N (%) / Mean ± SD / N / Median (IQR) or N (%) / Mean ± SD / N / Median (IQR) or N (%) / Mean ± SD
Age, years / 145 / 58.0 (44.0-67.0) / 56.9 ± 15.9 / 112 / 58.0 (45.8-70.0) / 57.3 ± 16.0 / 76 / 59.0 (45.8-72.0) / 58.3±17.1
Gender: Male/Female / 146 / 90 (62%)/56 (38)% / 113 / 70 (62%)/43 (38)% / 77 / 47 (61%)/30 (39%)
Height, cm / 140 / 169 (165-178) / 170 ± 8.9 / 107 / 169 (165-176) / 170 ± 8.1 / 72 / 169 (165-175) / 170±7.9
Weight, kg / 145 / 74 (60-87) / 76 ± 19.7 / 112 / 73 (60-84) / 75 ± 19.3 / 76 / 73 (60-81.5) / 74±19.1
Etiology of renal failure
Diabetes mellitus type 2 / 146 / 22 (15%) / 113 / 15 (13%) / 77 / 11 (14%)
Hypertension/vascular / 146 / 40 (27%) / 113 / 31 (27%) / 77 / 23 (30%)
Polycystic kidney disease / 146 / 10 (7%) / 113 / 7 (6%) / 77 / 7 (9%)
Unknown / 146 / 11 (8%) / 113 / 9 (8%) / 77 / 6 (8%)
Glomerulonephritis / 146 / 27 (18%) / 113 / 20 (18%) / 77 / 9 (12%)
Tumor / 146 / 0 (0%) / 113 / 0 (0%) / 77 / 0 (0%)
Interstitial nephropathy / 146 / 8 (5%) / 113 / 8 (7%) / 77 / 3 (4%)
Other / 146 / 28 (19%) / 113 / 23 (20%) / 77 / 18 (23%)
Other medical history
Cardiovascular disease / 146 / 76 (52%) / 113 / 56 (50%) / 77 / 40 (52%)
Diabetes / 146 / 38 (26%) / 113 / 29 (26%) / 77 / 18 (23%)
Kidney transplantation / 146 / 25 (17%) / 113 / 15 (13%) / 77 / 10 (13%)
Parathyroidectomy / 146 / 2 (1%) / 113 / 2 (2%) / 77 / 1 (1%)
Dialysis vintage (days) / 146 / 106 (33-229) / 140 ± 119 / 113 / 92 (33-213) / 129 ± 110 / 77 / 99 (30-213)
Dialysis vintage <6 months / 146 / 93 (64%) / 113 / 77 (68%) / 77 / 52 (68%)
Dialysis vintage >6 months / 146 / 53 (36%) / 113 / 36 (32%) / 77 / 25 (32%)
Laboratory parameters
iPTH, pg/mL / 113 / 611 (443-855) / 726 ± 437 / 90 / 633 (467-903) / 760 ± 463 / 77 / 611 (444-856) / 727±396
iPTH <300 pg/mL* / 146 / 6 (4%) / 113 / 4 (4%) / 77 / 3 (4%)
iPTH 300-499 pg/mL* / 146 / 33 (23%) / 113 / 25 (22%) / 77 / 24 (31%)
iPTH 500-800 pg/mL* / 146 / 39 (27%) / 113 / 30 (27%) / 77 / 26 (34%)
iPTH >800 pg/mL* / 146 / 35 (24%) / 113 / 31 (27%) / 77 / 24 (31%)
N/A* / 146 / 33 (23%) / 113 / 23 (20%) / - / -
Phosphorus, mmol/L / 124 / 2.05 (1.70-2.48) / 2.17 ± 0.68 / 98 / 2.07 (1.70-2.46) / 2.18 ± 0.68 / 72 / 2.07 (1.80-2.45) / 2.18±0.65
Calcium, total, mmol/L / 101 / 2.20 (2.05-2.33) / 2.20 ± 0.23 / 81 / 2.21 (2.04-2.33) / 2.20 ± 0.23 / 61 / 2.20 (2.05-2.28) / 2.17±0.20
Albumin, g/L / 35 / 40.0 (36.5-42.0) / 39.0 ± 4.6 / 29 / 40.0 (37.0-42.0) / 39.2 ± 4.9 / 23 / 40.0 (36.0-41.5) / 38.7±4.9
Calcium (corrected), mmol/L** / 36 / 2.33 (2.22-2.44) / 2.33 ± 0.17 / 30 / 2.33 (2.21-2.49) / 2.34 ± 0.18 / 24 / 2.32 (2.17-2.44) / 2.31±0.15
Ca (corr) x P, mmol2/L2 / 36 / 4.36 (3.72-5.03) / 4.67 ± 1.38 / 30 / 4.46 (3.73-5.58) / 4.80 ± 1.45 / 24 / 4.75 (3.78-5.74) / 4.85±1.30
Dialysate calcium, mmol/L / 146 / 1.50 (1.25-1.50) / 1.40 ± 0.14 / 113 / 1.50 (1.25-1.50) / 1.39 ± 0.13 / 77 / 1.50 (1.25-1.50) / 1.40±0.13
Concomitant medications
Phosphate binder / 146 / 120 (82%) / 95 (84%) / 77 / 63 (82%)
Calcium-based binder / 146 / 52 (36%) / 39 (35%) / 77 / 27 (35%)
Aluminium-based binder / 146 / 14 (10%) / 12 (11%) / 77 / 6 (8%)
Sevelamer / 146 / 72 (49%) / 57 (50%) / 77 / 38 (49%)
Lanthanum / 146 / 12 (8%) / 11 (10%) / 77 / 8 (10%)
Vitamin D sterols / 146 / 97 (66%) / 84 (74%) / 77 / 59 (77%)

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Table S2. Sensitivity analysis for percentage of patients below, within and above K/DOQI target for iPTH showing FAS (n=146), EAS (n=113) and CAS (n=77)

CAS complete analysis set; EAS evaluable analysis set; FAS full analysis set; iPTH intact parathyroid hormone

FAS / Month -6 / Baseline / Month 12
Below / 8% / 2% / 26%
Target / 16% / 4% / 36%
Above / 76% / 95% / 38%
EAS / Month -6 / Baseline / Month 12
Below / 11% / 1% / 26%
Target / 14% / 3% / 38%
Above / 76% / 96% / 36%
CAS / Month -6 / Baseline / Month 12
Below / 17% / 0% / 25%
Target / 17% / 4% / 36%
Above / 65% / 96% / 39%

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Table S3. Sensitivity analysis for phosphate binder and vitamin D usage

CAS complete analysis set; EAS evaluable analysis set; FAS full analysis set

FAS / EAS / CAS
Number (%) of patients / Number (%) of patients / Number (%) of patients
-6months / Baseline / 12 months / -6months / Baseline / 12 months / -6months / Baseline / 12 months
n=146 / n=146 / n=121 / n=113 / n=113 / n=113 / n=77 / n=77 / n=77
Phosphate binder / 81 (55%) / 120 (82%) / 106 (88%) / 62 (55%) / 95 (84%) / 98 (87%) / 40 (52%) / 63 (82%) / 67 (87%)
Calcium-based binder* / 51 (35%) / 52 (36%) / 35 (29%) / 36 (32%) / 39 (35%) / 32 (28%) / 25 (32%) / 27 (35%) / 22 (29%)
Aluminium-based binder* / 10 (7%) / 14 (10%) / 16 (13%) / 9 (8%) / 12 (11%) / 16 (14%) / 4 (5%) / 6 (8%) / 6 (8%)
Sevelamer* / 37 (25%) / 72 (49%) / 76 (63%) / 29 (26%) / 57 (50%) / 69 (61%) / 20 (26%) / 38 (49%) / 50 (65%)
Lanthanum* / 3 (2%) / 12 (8%) / 17 (14%) / 3 (3%) / 11 (10%) / 17 (15%) / 3 (4%) / 8 (10%) / 15 (19%)
Ca-based + sevelamer / 12 (8%) / 14 (10%) / 12 (10%) / 8 (7%) / 9 (8%) / 9 (10%) / 7 (9%) / 6 )8%) / 8 (10%)
Ca-based + Al-based / 3 (2%) / 3 (2%) / 3 (2%) / 2 (2%) / 2 (2%) / 3 (3%) / 2 (3%) / 2 (3%) / 2 (3%)
Sevelamer + Al-based / 3 (2%) / 5 (3%) / 11 (9%) / 3 (3%) / 5 (4%) / 11 (10%) / 1 (1%) / 2 (3%) / 4 (5%)
Vitamin D sterols / 64 (44%) / 97 (66%) / 89 (74%) / 52 (46%) / 84 (74%) / 85 (75%) / 36 (47%) / 59 (77%) / 61 (79%)
Calcitriol / 42 (29%) / 74 (51%) / 63 (52%) / 36 (32%) / 63 (56%) / 61 (54%) / 27 (35%) / 43 (56%) / 43 (56%)
Alfacalcidol / 20 (14%) / 18 (12%) / 14 (12%) / 14 (12%) / 16 (14%) / 14 (12%) / 8 (10%) / 12 (16%) / 12 (16%)
Paricalcitol / 2 (1%) / 5 (3%) / 12 (10%) / 2 (2%) / 5 (4%) / 10 (9%) / 1 (1%) / 4 (5%) / 6 (8%)

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Figure S1. Sensitivity analysis for iPTH over time

CAS complete analysis set; EAS evaluable analysis set; FAS full analysis set; iPTH intact parathyroid hormone

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Figure S2. Sensitivity analysis for cinacalcet dose over time

CAS complete analysis set; EAS evaluable analysis set; FAS full analysis set

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KDIGO target achievement

Figure S3. Percentage of patients achievingKDIGO targets for iPTH (120-600 pg/mL), Phosphorus (1.13-1.48 mmol/L) and Calcium (total; 2.1-2.4 mmol/L), based on ‘normal’ values from an Austrian registry (1). BL baseline (timepoint at which cinacalcet was initiated), Ca calcium, iPTH intact parathyroid hormone, M = month, P phosphorus

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Total Calcium

Table S4. Evolution of total Ca (mmol/L): median (Q1, Q3)

Month / Mild / Moderate / Severe
N / Ca / N / Ca / N / Ca
-6 / 10 / 2.16
(2.09-2.22) / 11 / 2.38
(2.26-2.47) / 12 / 2.23
(2.15-2.40)
-3 / 14 / 2.18
(2.07-2.29) / 22 / 2.25
(2.15-2.33) / 14 / 2.22
(2.01-2.42)
0 / 21 / 2.17
(2.03-2.31) / 21 / 2.21
(2.13-2.23) / 26 / 2.22
(2.04-2.41)
3 / 21 / 2.17
(2.05-2.23) / 22 / 2.11
(1.95-2.19) / 25 / 2.04
(1.91-2.18)
6 / 20 / 2.12
(1.95-2.25) / 20 / 2.09
(1.94-2.16) / 25 / 2.10
(1.95-2.24)
9 / 21 / 2.09
(1.97-2.21) / 19 / 2.01
(1.96-2.20) / 25 / 2.08
(1.94-2.30)
12 / 20 / 2.09
(2.01-2.16) / 20 / 2.15
(2.09-2.25) / 21 / 2.06
(1.97-2.24)

References

1.Kramar R. Österreichisches Dialyse- und Transplantationsregister, ÖDTR, Jahresbericht 2012 der Österreichischen Gesellschaft für Nephrologie 2013 [cited 2014 30 April]. Available from:

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