Chronic Kidney Disease, Secondary Hyperparathyroidism
Conditions
Keywords
PTH, Active Vitamin D, hypercalcemia, Chronic Kidney Disease
Brief summary
Secondary Hyperparathyroidism (SHPT) occurs in many patients with kidney disease and leads to bone disease. Active forms of vitamin D, calcitriol and paricalcitol, treat SHPT, but may have different effects on blood calcium. This study will randomize patients with SHPT and stage 3 or 4 CKD to treatment with calcitriol or paricalcitol, and monitor patients for the incidence of high blood calcium, and effectiveness of SHPT treatment.
Detailed description
General Design * Open label, active comparator, multicenter, parallel group, phase 4 study of paricalcitol versus calcitriol for suppression of PTH in stage 3 and 4 CKD patients with SHPT. * Total study duration is 26 weeks (1 week screening, 24 weeks active medications, 1 week follow up. * Patients meeting inclusion/exclusion criteria including baseline laboratory results will be randomized to paricalcitol or calcitriol, and enter a 24 weeks treatment phase. Visits, including safety and efficacy laboratory tests will be at weeks 4, 8, 12, 18, and 24. A follow up visit will be performed 1 week after stopping study medication.
Interventions
DRUGParicalcitol
1 mcg daily, adjusted to achieve 40-60% PTH suppression
DRUGCalcitriol
0.25 mcg daily, adjusted to achieve 40-60% PTH suppression
Sponsors
Henry Ford Hospital
Northwestern University Feinberg School of Medicine
Endeavor Health
Abbott
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18; Able to give informed consent 2. Chronic kidney disease, and estimated GFR 15 to 60 ml/min using the abbreviated MDRD equation 3. intact PTH (iPTH) \>120 pg/ml at baseline 4. albumin corrected calcium \> 8.5 mg/dL to \< 10.0 mg/dL at baseline 5. Phosphorus \< 4.6 mg/dL at baseline 6. If on a phosphorus binder; no change in dose within the 4 weeks prior to screening
Exclusion criteria
1. Receiving any active form of vitamin D within 4 weeks prior to screening (calcitriol, doxercalciferol; paricalcitol; alfacalcidol) 2. Receiving \>50,000 IU per month of ergocalciferol or \> 1000 IU of cholecalciferol per day within the previous 30 days. 3. history of primary HPT 4. On prednisone \> 30 days within the previous 6 months 5. receiving bisphosphonates or calcitonin within the previous 12 months 6. Non-elective hospitalization within the previous 30 days. 7. Expected to initiate dialysis or receive a kidney transplant within the next 6 mo. 8. History of renal or other organ transplant 9. History of parathyroidectomy or previous diagnosis of primary hyperparathyroidism 10. Receiving cinacalcet within 4 weeks prior to screening. 11. An active drug/alcohol dependence or abuse history 12. History of non-compliance with visits or medications that preclude study compliance in the opinion of the investigator 13. Pregnant, or able to become pregnant and unwilling to use a birth control method considered reliable by the principal investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Hypercalcemia | 24 week treatment period | Serum Calcium 10.5 mg/dL or higher, confirmed by repeat measurement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paricalcitol titrated to achieve 40-60% PTH suppression
Paricalcitol: 1 mcg daily, adjusted to achieve 40-60% PTH suppression | 54 |
| Calcitriol titrated to achieve 40-60% PTH suppression
Calcitriol: 0.25 mcg daily, adjusted to achieve 40-60% PTH suppression | 56 |
| Total | 110 |
Baseline characteristics
| Characteristic | Calcitriol | Total | Paricalcitol |
|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 12.6 | 65.6 years STANDARD_DEVIATION 12.9 | 66.6 years STANDARD_DEVIATION 13.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 41 Participants | 74 Participants | 33 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 | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 14 Participants | 32 Participants | 18 Participants |
| Sex: Female, Male Female | 30 Participants | 54 Participants | 24 Participants |
| Sex: Female, Male Male | 26 Participants | 56 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 53 | 12 / 54 |
| serious Total, serious adverse events | 0 / 53 | 1 / 54 |
Outcome results
Primary
Confirmed Hypercalcemia
Serum Calcium 10.5 mg/dL or higher, confirmed by repeat measurement.
Time frame: 24 week treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol | Confirmed Hypercalcemia | 3 participants |
| Calcitriol | Confirmed Hypercalcemia | 1 participants |
p-value: 0.36Fisher Exact