Chronic Kidney Disease, Coronary Calcification, Disorders of Calcium and Bone Metabolism, Vitamin D Deficiency
Conditions
Keywords
Secondary Hyperparathryoidism, Chronic Kidney Disease, Vitamin D, Coronary Calcification, Bone metabolism
Brief summary
Patients with chronic kidney disease (CKD) have a higher mortality rate than the general population, with cardiovascular disease (CVD) accounting for approximately 50% of deaths. Vascular calcification is a common finding in patients with CKD. Furthermore, patients with CKD develop secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Treatment of secondary hyperparathyroidism includes use of activated vitamin D including calcitriol and paricalcitol. Recent evidence in dialysis patients suggest an improved survival in patients using paricalcitol compared to calcitriol. Studies in uremic rats suggests that there are differential effects of calcitriol and paricalcitol in expression of markers of soft-tissue calcification independent of calcium-phosphorus product. Calcitriol increased calcification of vascular smooth muscle cells cultured in calcification media. There was also significant increase in pulse pressure in animals treated with calcitriol. The investigators hypothesize that these different forms of vitamin D may have differential effects in vascular calcification progression in CKD patients.
Detailed description
Coronary artery calcification (CAC) is a risk marker for CVD and mortality. In animal models, calcitriol significantly increased the serum calcium-phosphate product and aortic calcium content, while paricalcitol had no effect. The objective of this randomized, blinded single-center is to determine the differential effect of oral calcitriol and paracalcitol on vascular calcification in patients with chronic kidney disease (CKD). We performed a total of 89 screening visits and randomized 44 participants. Forty participants completed the final visit. Diagram 1 presents the recruitment schematic.
Interventions
DRUGCalcitriol (Rocaltrol®)
Subjects taking calcitriol will be started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then calcitriol will be increased to 0.5 mcg 3x/week.
DRUGParicalcitol
Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then paricalcitol will be increased to 4 mcg 3x/week.
Sponsors
Abbott
Joslin Diabetes Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CKD stages 3 or 4 (estimated glomerular filtration rate (eGFR) between 15 and 59) * Diagnosis of secondary hyperparathyroidism, which is defined as: * Elevated intact PTH (iPTH) as per KDIGO guidelines: * CKD stage 3 (eGFR 30-59) or CKD stage 4 (eGFR 15-29) with iPTH \> Upper Limit of Normal for lab (6.8 pmol/L) * Presence of Coronary Artery Calcium (CAC \> 0) * Subject will be able to complete the study, to the best of his/her knowledge
Exclusion criteria
* iPTH \>1500 pg/ml * Current or previous use of bisphosphonates * History of parathyroidectomy or anticipated parathyroidectomy * History of cinacalcet use * History of a solid organ transplant or scheduled date for transplant surgery * History of coronary revascularization (coronary artery bypass surgery or percutaneous intervention) * History of coronary artifact (e.g. pacemaker, intracardiac defibrillator, artificial valve or biventricular leads) * Active atrial fibrillation * Weight greater than 300 pounds (due to limitations of equipment) * HIV positive * Current pregnancy (although pregnancy is very rare in the CKD population) * Life expectancy less than two years as judged by primary physician * Institutionalized patients (nursing home or prisoners) * Language barrier or mental incapacity to consent * Inability to swallow tablets or current gastrointestinal disorder that may be associated with impaired absorption of orally administered medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Artery (CAC) Score Progression | 48 weeks | coronary artery (CAC) score difference between baseline and followup CT scans. It was measured in Agatston units. These are units of amount of calcification in the blood vessels so it's a continuous variable. The amount of calcium was quantified with the Agatston scoring method. Calcium scores were adjusted with a standard calcium phantom that was scanned along with the participant. The phantom contained known calcium density bars and provided a way to calibrate the x-ray attenuation level. Participants scoring CAC \>400 are considered to be at risk for having at least one coronary lesion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcitriol Calcitriol (Rocaltrol®): Subjects taking calcitriol will be started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then calcitriol will be increased to 0.5 mcg 3x/week. | 22 |
| Paricalcitol Paricalcitol: Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then paricalcitol will be increased to 4 mcg 3x/week. | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Calcitriol | Total | Paricalcitol |
|---|---|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 7.4 | 65.6 years STANDARD_DEVIATION 9.3 | 65.5 years STANDARD_DEVIATION 11 |
| 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 | 14 Participants | 29 Participants | 15 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment United States | 22 participants | 44 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 18 Participants | 13 Participants |
| Sex: Female, Male Male | 17 Participants | 26 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 22 | 1 / 22 |
| other Total, other adverse events | 18 / 22 | 20 / 22 |
| serious Total, serious adverse events | 9 / 22 | 8 / 22 |
Outcome results
Primary
Coronary Artery (CAC) Score Progression
coronary artery (CAC) score difference between baseline and followup CT scans. It was measured in Agatston units. These are units of amount of calcification in the blood vessels so it's a continuous variable. The amount of calcium was quantified with the Agatston scoring method. Calcium scores were adjusted with a standard calcium phantom that was scanned along with the participant. The phantom contained known calcium density bars and provided a way to calibrate the x-ray attenuation level. Participants scoring CAC \>400 are considered to be at risk for having at least one coronary lesion.
Time frame: 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol | Coronary Artery (CAC) Score Progression | 74.38 Agatston units | Standard Deviation 110.39 |
| Paricalcitol | Coronary Artery (CAC) Score Progression | 106.32 Agatston units | Standard Deviation 126.06 |