End Stage Renal Disease
Conditions
Brief summary
A few studies have reported erythropoiesis-stimulating agent (ESA) doses before and after 25D supplementation, but only one of these is a prospective clinical trial, and it is a small, single center study lacking a control arm. The investigators propose to conduct a double blind, randomized, placebo controlled clinical trial of ergocalciferol supplementation to confirm safety and determine effects on Erythropoietin (EPO) dosing, active D dosing, and mineral metabolic parameters in hemodialysis patients.
Interventions
DIETARY_SUPPLEMENTergocalciferol supplementation
50,000 IU given either weekly; weekly for 3 months then monthly for 3 months; monthly
OTHERplacebo
placebo pill given weekly, weekly for 3 months then monthly for 3 months; monthly
Sponsors
Dialysis Clinic, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients treated with thrice weekly in-center hemodialysis (HD) for more than 90 days. 2. Treated with EPO for at least 90 days. The mode of administration, intravenous (IV) or subcutaneous (SC), must remain the same for 90 days prior to enrollment. 3. The method by which EPO is prescribed (per DCI Corporate or local protocol or per physician on an individualized basis) must remain the same for at least 90 days prior to enrollment with respect to the ceiling for the total EPO dose administered per week, if a ceiling is used, and the level of hemoglobin (Hgb) at which EPO is discontinued (Hgb cutoff), if a Hgb cutoff is used. 4. The method by which IV Iron is prescribed (per DCI Corporate or local protocol or per physician on an individualized basis) must remain the same for at least 90 days prior to enrollment with respect to the serum ferritin and transferrin saturation (TSAT) targeted, if specific ferritin and TSAT targets are used
Exclusion criteria
1. Patients with a serum calcium ≥10.5 mg/dL on at least one occasion in the past 30 days. 2. Patients with a serum phosphorus \>8.0 mg/dL on at least one occasion in the past 30 days. 3. Active infection defined by the use of IV antibiotic use within the past 30 days. 4. Current use of immunosuppressant medications other than low dose corticosteroids (prednisone \<10 mg per day or equivalent) 5. History of a hematological malignancy (e.g. multiple myeloma, leukemia). 6. Sickle cell disease (sickle cell trait is not an exclusion). 7. Myelodysplasia requiring 1 or more blood transfusions in the past 3 months. 8. Transfusion for any reason within the past 30 days. 9. Medical conditions that cause a reduction in the absorption of oral vitamin D including Crohn's disease, celiac sprue, cystic fibrosis and surgical removal of part or all of the stomach or intestine. 10. Medications that cause a reduction in the absorption of oral vitamin D including cholestyramine (Questran, others), colestipol (Colestid, others) and orlistat (Xenical, Alli). 11. Known allergy/adverse reaction to ergocalciferol. 12. Treated with ergocalciferol and/or cholecalciferol (except if part of a multi-vitamin) within the last 3 months. 13. Average Kt/V \< 1.3 on past three monthly labs. There must be at least 2 monthly Kt/V values in the past three months. 14. Skipped more than 3 dialysis treatments (excluding planned missed treatments) within the past 3 months for reasons other than hospitalization. 15. Life expectancy less than 6 months. 16. Kidney transplantation planned in the next 6 months. 17. Switch to peritoneal dialysis planned in the next 6 months. 18. Pregnant or planning to become pregnant within the next 6 months. A pre-menopausal woman must agree to use contraception for the duration of the study. If a woman has not had menses in over 12 months, consider this patient to be menopausal. 19. Unable or unwilling to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EPO Dose | Baseline, 6 months | The primary outcome is the change in the median EPO dose from baseline to 6 months after ergocalciferol supplementation. |
Countries
United States
Participant flow
Pre-assignment details
470 subjects were enrolled in the study; however 151 subjects did not make it to randomization due to EPO criteria not met n=45, did not meet other inclusion criteria n=57, no was reason provided n=49. Of the 319 subjects randomized, 43 had a baseline 25(OH)D \>30. This analysis only pertains to the 276 subjects with a baseline 25(OH)D ≤30.
Participants by arm
| Arm | Count |
|---|---|
| Ergocalciferol Supplementation ergocalciferol supplementation: 50,000 IU given either weekly; weekly for 3 months then monthly for 3 months; monthly | 137 |
| Placebo placebo: placebo pill given weekly, weekly for 3 months then monthly for 3 months; monthly | 139 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 4 |
| Overall Study | GI symptoms | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Transplant | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Ergocalciferol Supplementation | Total | Placebo |
|---|---|---|---|
| 25Vit D (ng/mL) | 16.0 ng/mL STANDARD_DEVIATION 5.9 | 16.4 ng/mL STANDARD_DEVIATION 6.2 | 16.9 ng/mL STANDARD_DEVIATION 6.4 |
| Age, Continuous | 61.4 years STANDARD_DEVIATION 13.3 | 61.1 years STANDARD_DEVIATION 13.6 | 60.8 years STANDARD_DEVIATION 13.9 |
| Epogen Dose, units/week | 5800 units/week | 5550 units/week | 5400 units/week |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 76 Participants | 166 Participants | 90 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 51 Participants | 92 Participants | 41 Participants |
| Region of Enrollment United States | 137 participants | 276 participants | 139 participants |
| Sex: Female, Male Female | 67 Participants | 125 Participants | 58 Participants |
| Sex: Female, Male Male | 70 Participants | 151 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 137 | 8 / 139 |
| serious Total, serious adverse events | 4 / 137 | 4 / 139 |
Outcome results
Primary
EPO Dose
The primary outcome is the change in the median EPO dose from baseline to 6 months after ergocalciferol supplementation.
Time frame: Baseline, 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ergocalciferol Supplementation | EPO Dose | EPO dose - Baseline | 5800 units/week |
| Ergocalciferol Supplementation | EPO Dose | EPO dose - 6 months | 7000 units/week |
| Placebo | EPO Dose | EPO dose - Baseline | 5400 units/week |
| Placebo | EPO Dose | EPO dose - 6 months | 6050 units/week |
p-value: 0.78Mixed Models Analysis