Dialysis, Secondary Hyperparathyroidism
Conditions
Keywords
Dialysis, Calcitriol Resistant, Secondary Hyperparathyroidism
Brief summary
The primary objective of this study is to evaluate the efficacy and safety of paricalcitol in participants with moderate to severe secondary hyperparathyroidism (SHPT) undergoing hemodialysis who are resistant to treatment with calcitriol.
Detailed description
This is a multi-center, prospective, open label, one arm, phase IV study designed to demonstrate paricalcitol efficacy and safety in the treatment of moderate to severe secondary hyperparathyroidism in calcitriol resistant participants on dialysis. Following screening, participants began an 8-week controlled calcitriol therapy period. Participants whose parathyroid hormone (PTH) levels decreased were to be discontinued from the study. Those whose PTH levels did not decrease began paricalcitol therapy using a dose calculated by 0.04 to 0.1 microgram per kilogram (mcg/kg). Paricalcitol was administered intravenously at anytime during the subjects' dialysis. The paricalcitol dose was to be titrated every 2 weeks until iPTH was reduced or up to 4 months, after which it was to be adjusted monthly for 1 year based on serum PTH, calcium, phosphorus, and albumin measurements.
Interventions
DRUGCalcitriol
Initial doses determined according to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guideline (Am J Kidney Dis 2003;42(4)Suppl 3:S1-S201). During therapy, calcitriol dose may be modified by 0.5 - 1 mcg at 2- to 4-week intervals.
DRUGParicalcitol
Dose calculated by 0.04 to 0.1 microgram per kilogram (mcg/kg). Paricalcitol will be administered intravenously after the participants' dialysis. The paricalcitol dose will be titrated every 2 weeks until iPTH presents a reduction or up to 4 months, after which it will be adjusted monthly based on serum PTH, calcium, phosphorus and albumin measurements. Dosing may be modified by 2-4 mcg increments at 2- to 4-week intervals.
Sponsors
Statistika Consultoria Ltda
Abbott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female participants \> 18 years of age, with chronic kidney disease (CKD) stage V; * Participants with diagnosis of calcitriol resistance defined as: Episodes of hypercalcemia and/or hyperphosphatemia (defined as an episode of calcium or phosphorus above Upper Limit of Normal or documented by medical history stating that the treatment with calcitriol was discontinued due to hypercalcemia and/or hyperphosphatemia) that precludes treatment continuation and/or persistent PTH above 600pg/mL during the calcitriol therapy; * PTH value at screening visit between 600 pg/mL and 2,000 pg/mL; * Stable clinical conditions; * Participant has voluntarily consented to participate in the study, by signing and dating an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and all his questions about the study have been elucidated. The informed consent must be signed before any study-specific procedures are performed.
Exclusion criteria
* Previous parathyroidectomy; * Presence of hypercalcemia (corrected Ca \> 10.5 mg/dL) and/or hyperphosphatemia (P \> 6.0 mg/dL) and/or Ca x P product \> 60, at screening visit (corrected Ca calculated by: \[4 - participant's serum albumin (g/dL)\] x 0.8 + participant's serum Ca value); * Severe and/or unstable clinical conditions, e.g., congestive heart failure, advanced cancer, advanced HIV disease, severe endocrinopathies, uncompensated diabetes mellitus, life-threatening cardiac arrhythmias, etc; * Abnormal liver tests (\> 1.5 times above upper limit of normal); * Pregnant or breast-feeding women; * Evidence of vitamin D toxicity; * Known hypersensitivity to any study drug components.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With a 50% Reduction in Parathyroid Hormone (PTH) Levels Relative to Visit 4 Values | Up to Week 24 | This outcome was measured at Visit 15, which could occur at different timepoints from study start, depending on the duration of each study period for each participant, relative to values on Visit 4. For participants who did not perform visit 4, the reduction of the PTH levels were to be assessed relative to visit 5 values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Bone Remodeling Markers Over Time | Every 3 months | Deoxypyridinoline and bone-specific alkaline phosphatase levels were to be measured every 3 months and changes over time analyzed using descriptive statistics. |
| Number of Participants With Adverse Events | Up to 1 year | The occurrence of adverse events was considered a secondary endpoint in this study. For details on adverse events that occurred prior to study termination, refer to the safety section below. |
Countries
Brazil
Participant flow
Pre-assignment details
After Screening, participants entered an 8-week controlled calcitriol period. Participants whose parathyroid hormone (PTH) levels decreased after 8 weeks (i.e., participants who were not resistant to calcitriol) were discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| Calcitriol Challenge Followed by Paricalcitol To confirm this resistance, participants began a controlled calcitriol therapy period. After this period, participants whose parathyroid hormone (PTH) levels were not reduced according to parameters in protocol were to begin a paricalcitol titration period of up to 4 months, followed by paricalcitol therapy for up to 1 year. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Calcitriol Challenge Followed by Paricalcitol |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Region of Enrollment Brazil | 13 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Proportion of Participants With a 50% Reduction in Parathyroid Hormone (PTH) Levels Relative to Visit 4 Values
This outcome was measured at Visit 15, which could occur at different timepoints from study start, depending on the duration of each study period for each participant, relative to values on Visit 4. For participants who did not perform visit 4, the reduction of the PTH levels were to be assessed relative to visit 5 values.
Time frame: Up to Week 24
Population: No efficacy analysis was performed in this study. At the time the study was stopped, 3 participants were receiving paricalcitol, but none of them had reached the time point for the primary analysis.
Secondary
Changes in Bone Remodeling Markers Over Time
Deoxypyridinoline and bone-specific alkaline phosphatase levels were to be measured every 3 months and changes over time analyzed using descriptive statistics.
Time frame: Every 3 months
Population: No efficacy analysis was performed in this study. At the time the study was stopped, 3 participants were receiving paricalcitol, but none of them had reached the time point for the secondary analysis.
Secondary
Number of Participants With Adverse Events
The occurrence of adverse events was considered a secondary endpoint in this study. For details on adverse events that occurred prior to study termination, refer to the safety section below.
Time frame: Up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Calcitriol Challenge Followed by Paricalcitol | Number of Participants With Adverse Events | 3 Participants |