Of the 376 enrolled patients, 174 (46.3%) initiated treatment with ERC (99.4% at a 30 mcg daily dose), 55 (14.6%) initiated treatment with AVD (80% received calcitriol at 0.25 mcg/ day, 11% received calcitriol at 0.50 mcg/day, 7% received doxercalciferol at 2.5 mcg/day and 2% received paricalcitol at 1.0 mcg/day) and 147 (39.1%) initiated treatment with NVD [weekly oral ergocalciferol (n = 97) or cholecalciferol (n = 50) at doses of ≥50,000 IU (64.7%), 14,000 to < 50,000 IU (23.1%) or 5000 to < 14,000 IU (12.2%) for ≥7 months (55.8%), 4–6 months (19.0%) or 1–3 months (25.2%)]. The mean (SD) age of the enrolled patients was 69.5 (13.2) years, mean body mass index (BMI) was 32.8(15.2) kg/m2, 50.8% were female, 88.8% non-Hispanic and 64.6% Caucasian. BMI was highest among the ERC cohort. ERC and AVD cohorts consisted of more CKD stage 4 patients than stage 3, while the reverse was true for the NVD cohort. Patient demographics and baseline characteristics for all three cohorts are presented in Table 1.

Evaluated treatment characteristics included length of prescription and dose titrations, as well as reasons for dose titrations. Most prescriptions had durations of more than 6 months (72.2%): the mean (SD) observed prescription length of ERC was 63.5 (36.5) weeks, 51.3 (33.6) weeks for AVD, and 41.5 (32.4) weeks for NVD. A few patients (1.7%) up-titrated dose in the ERC cohort (from 30 to 60 mcg/day) but patients in the AVD and NVD cohorts maintained a constant dose throughout the study.

In the ERC cohort, the baseline 25D and PTH levels averaged 20.3 ± 0.7 (SE) ng/mL and 181.4 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL or 18.8% (p < 0.001) without significant impact on serum Ca and P levels. Serum total alkaline phosphatase (ALP) trended downwards. Additionally, eGFR decreased 3.1 ± 0.7 mL/min/1.73m2 (p < 0.001). Mean follow-up times for these laboratory parameters ranged from 23.4 to 28.8 weeks (Table 2). Normalized for duration of the follow-up (mean 28.1 weeks), the mean eGFR decrease per patient-week was 0.11 mL/min/1.73m2.

In the AVD cohort, baseline 25D and PTH levels averaged 23.5 ± 1.0 (SE) ng/mL and 156.9 ± 9.7 pg/mL, respectively. Serum 25D rose by 5.5 ± 1.3 ng/mL (P < 0.001) without statistically significant impact on PTH and serum P levels. Serum total ALP trended downwards. Additionally, serum Ca levels elevated by 0.2 ± 0.1 mg/dL (p < 0.001) and eGFR decreased by 1.6 ± 0.6 mL/min/1.73m2 (p < 0.01). Mean follow-up times ranged from 21.3 to 24.5 weeks (Table 2). Normalized for duration of the follow-up (mean 21.4 weeks), the mean eGFR decrease per patient-week was 0.08 mL/min/1.73m2.

In the NVD cohort, baseline 25D and PTH levels averaged 18.8 ± 0.6 (SE) ng/mL and 134.8 ± 6.8 pg/mL, respectively. Serum 25D increased by 9.7 ± 1.5 ng/mL (p < 0.001) without significant impact on PTH or serum Ca and P levels. Serum total ALP trended upwards. Additionally, eGFR decreased 1.2 ± 0.6 mL/min/1.73m2 (p < 0.05). Mean follow-up times ranged from 18.3 to 21.1 weeks (Table 2). Normalized for duration of the follow-up (mean 20.0 weeks), the mean eGFR per patient-week decrease was 0.07 mL/min/1.73m2.

There were no statistically significant differences in the normalized eGRF decline between groups. Some variations in results were identified within subgroups of the ERC, AVD and NVD cohorts. African-Americans experienced less clinical effectiveness compared to non-African Americans. Among patients with diabetes, hypertension, anemia, or hyperlipidemia, those with comorbidities faced worse clinical effectiveness compared to those without. Across all groups, patients below the BMI threshold of 30 for obesity saw more clinical effectiveness than those above, though ERC was still the most effective of the three treatments for those with higher BMI values.

Additional analyses were conducted to determine effectiveness of therapies based on main parameters of interest (Fig. 2). Within the ERC cohort, 70.1% (n = 122) of patients achieved 25D levels of ≥30 ng/mL at follow-up, compared to 43.6% (n = 24) and 36.7% (n = 54) in the AVD and NVD cohorts, respectively (p < 0.001 compared to ERC). Among ERC-treated patients that started at a baseline 25D level of < 20 ng/mL, 58.9% (n = 53) of patients achieved a 25D level of ≥30 n/mL by follow-up, compared to 21.4% (n = 3) and 26.1% (n = 23) in the AVD and NVD cohorts, respectively (p < 0.05 or 0.001 compared to ERC). In regard to achievement of a ≥ 30% reduction in PTH over the duration of the study, 40.2% (n = 70) of ERC-treated patients achieved this endpoint, compared to 21.8% (n = 12) and 15.0% (n = 22) in the AVD and NVD cohorts, respectively (p < 0.05 or 0.001 compared to ERC).

Primary Analysis – Key Endpoints

In addition, the ERC cohort had a much greater percentage of patients achieving 25D levels of at least 50 ng/mL than the AVD and NVD cohorts (51.6, 12.5, and 18.5%, respectively), which may help explain the observed differences in PTH reduction between cohorts.