Cardiac Morbidity, Chronic Kidney Disease Stage V, Secondary Hyperparathyroidism
Conditions
Keywords
Secondary Hyperparathyroidism (sHPT), Paricalcitol, Chronic kidney disease stage 5 (CKD stage 5)
Brief summary
The purpose of this study was to ascertain the percentage of cardiac patients with chronic kidney disease (CKD) stage 5 treated with paricalcitol IV achieving intact parathyroid hormone (iPTH) levels in target range of Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines (150 - 300 pg/mL) after 2 years.
Detailed description
Secondary hyperparathyroidism (SHPT) is a frequent complication in patients with chronic kidney disease (CKD) stage 5 receiving dialysis. SHPT is an adaptive response to CKD and is characterized by an elevation in parathyroid hormone (PTH) and consecutively high calcium levels. Elevations in calcium levels, phosphate levels, and PTH are correlated with CKD disease progression as well as development or aggravation of cardiovascular impairment. Many CKD patients cannot be treated well with Vitamin D analogues because of effects on calcium. Hypercalcemia is a well - known factor for cardiac disease. No data are available in Austria for a cohort with cardiac disease treated with Zemplar (paricalcitol IV).
Interventions
None listed
Sponsors
Assign Data Management and Biostatistics GmbH
AbbVie (prior sponsor, Abbott)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged at least 18 years * Patients with secondary hyperparathyroidism associated with CKD stage 5, serum iPTH \> 150 pg/mL, * Cardiac disease as described by Medical Dictionary for Regulatory Activities (MedDRA) terms: * cardiac disorder as cardiac arrhythmias * cardiac disorder signs and symptoms * cardiac neoplasm * cardiac valve disorder * heart failures * myocardial disorder * pericardial disorder * Serum phosphate level \< 6.5 mg/dL and serum calcium level \< 10.5 mg/dL
Exclusion criteria
* Patients who meet contraindications as outlined in the latest version of Zemplar (Paricalcitol IV) summary of product characteristics * Patients with known hypersensitivity to paricalcitol or any component of the formulation, vitamin D intoxication, hypercalcemia; cinacalcet as concomitant medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Baseline and Months 3, 6, 12, 18, and 24 | Target range of intact parathyroid hormone was defined according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines as between 15.9 - 31.8 pmol/L (150 to 300 pg/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hyperphosphatemia | Baseline and Months 3, 6, 12, 18, and 24 | Hyperphosphatemia was defined as a phosphate value of \> 2.1 mmol/L (6.5 mg/dL) in one measurement. Serum phosphate was measured at every study visit. |
| Percentage of Participants With at Least a 30%-Reduction in iPTH Levels | Baseline and Months 3, 6, 12, 18, and 24 | The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) levels from Baseline level. |
| Percentage of Participants With at Least 30%-Reduction in iPTH Levels in at Least Two Consecutive Measurements | Baseline to Month 24 | The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) level from Baseline in at least 2 consecutive visits. |
| Percentage of Participants With Hypercalcemia | Baseline and Months 3, 6, 12, 18, and 24 | Hypercalcemia was defined as a calcium value of \> 2.625 mmol/L (10.5 mg/dL) in one measurement. Serum calcium was measured at every study visit. |
| Percentage of Participants Experiencing Hospitalization | 24 months | The percentage of participants with at least one hospitalization, at least one cardiac-related hospitalization and at least one non-cardiac-related hospitalization during the course of the study. |
| Number of Participants With Cardiac Disease Progression | Month 3, 6, 12, 18, and 24 | Cardiac disease progression was determined by the Investigator. |
| Percentage of Participants With at Least One Concomitant Medication | 24 months | The percentage of participants with at least one concomitant medication during the course of the study, by the following types: * Phosphate binder * Epoetin * Renin-Angiotensin-Aldosterone System (RAAS) inhibitors * Cinacalcet * Other |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paricalcitol IV Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years. | 67 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 14 |
| Overall Study | Kidney transplant | 10 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Low parathyroid hormone levels | 8 |
| Overall Study | Serious adverse event | 2 |
Baseline characteristics
| Characteristic | Paricalcitol IV |
|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 13.8 |
| Blood Pressure Diastolic | 75.1 mm Hg STANDARD_DEVIATION 11.5 |
| Blood Pressure Systolic | 137.2 mm Hg STANDARD_DEVIATION 19.4 |
| Region of Enrollment Austria | 67 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 67 |
| serious Total, serious adverse events | 31 / 67 |
Outcome results
Primary
Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range
Target range of intact parathyroid hormone was defined according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines as between 15.9 - 31.8 pmol/L (150 to 300 pg/mL).
Time frame: Baseline and Months 3, 6, 12, 18, and 24
Population: Intent-to-treat population; last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Baseline | 28.4 percentage of participants |
| Paricalcitol IV | Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Month 3 | 43.3 percentage of participants |
| Paricalcitol IV | Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Month 6 | 35.8 percentage of participants |
| Paricalcitol IV | Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Month 12 | 38.8 percentage of participants |
| Paricalcitol IV | Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Month 18 | 37.3 percentage of participants |
| Paricalcitol IV | Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range | Month 24 | 35.8 percentage of participants |
Secondary
Number of Participants With Cardiac Disease Progression
Cardiac disease progression was determined by the Investigator.
Time frame: Month 3, 6, 12, 18, and 24
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Number of Participants With Cardiac Disease Progression | Month 3 | 2 participants |
| Paricalcitol IV | Number of Participants With Cardiac Disease Progression | Month 6 | 2 participants |
| Paricalcitol IV | Number of Participants With Cardiac Disease Progression | Month 12 | 4 participants |
| Paricalcitol IV | Number of Participants With Cardiac Disease Progression | Month 18 | 0 participants |
| Paricalcitol IV | Number of Participants With Cardiac Disease Progression | Month 24 | 0 participants |
Secondary
Percentage of Participants Experiencing Hospitalization
The percentage of participants with at least one hospitalization, at least one cardiac-related hospitalization and at least one non-cardiac-related hospitalization during the course of the study.
Time frame: 24 months
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Percentage of Participants Experiencing Hospitalization | Hospitalizations | 41.8 percentage of participants |
| Paricalcitol IV | Percentage of Participants Experiencing Hospitalization | Cardiac-related hospitalizations | 14.9 percentage of participants |
| Paricalcitol IV | Percentage of Participants Experiencing Hospitalization | Non-cardiac-related hospitalizations | 37.3 percentage of participants |
Secondary
Percentage of Participants With at Least 30%-Reduction in iPTH Levels in at Least Two Consecutive Measurements
The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) level from Baseline in at least 2 consecutive visits.
Time frame: Baseline to Month 24
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol IV | Percentage of Participants With at Least 30%-Reduction in iPTH Levels in at Least Two Consecutive Measurements | 44.8 percentage of participants |
Secondary
Percentage of Participants With at Least a 30%-Reduction in iPTH Levels
The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) levels from Baseline level.
Time frame: Baseline and Months 3, 6, 12, 18, and 24
Population: Intent-to-treat; LOCF was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Percentage of Participants With at Least a 30%-Reduction in iPTH Levels | Month 3 | 41.8 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least a 30%-Reduction in iPTH Levels | Month 6 | 40.3 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least a 30%-Reduction in iPTH Levels | Month 12 | 47.8 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least a 30%-Reduction in iPTH Levels | Month 18 | 52.2 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least a 30%-Reduction in iPTH Levels | Month 24 | 47.8 percentage of participants |
Secondary
Percentage of Participants With at Least One Concomitant Medication
The percentage of participants with at least one concomitant medication during the course of the study, by the following types: * Phosphate binder * Epoetin * Renin-Angiotensin-Aldosterone System (RAAS) inhibitors * Cinacalcet * Other
Time frame: 24 months
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Percentage of Participants With at Least One Concomitant Medication | Phosphate binder | 80.6 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least One Concomitant Medication | Epoetin | 68.7 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least One Concomitant Medication | RAAS Inhibitor | 43.3 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least One Concomitant Medication | Cinacalcet | 13.4 percentage of participants |
| Paricalcitol IV | Percentage of Participants With at Least One Concomitant Medication | Other | 86.6 percentage of participants |
Secondary
Percentage of Participants With Hypercalcemia
Hypercalcemia was defined as a calcium value of \> 2.625 mmol/L (10.5 mg/dL) in one measurement. Serum calcium was measured at every study visit.
Time frame: Baseline and Months 3, 6, 12, 18, and 24
Population: Intent-to-treat; LOCF was used
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Percentage of Participants With Hypercalcemia | Baseline | 0.0 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hypercalcemia | Month 3 | 0.0 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hypercalcemia | Month 6 | 0.0 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hypercalcemia | Month 12 | 1.5 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hypercalcemia | Month 18 | 0.0 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hypercalcemia | Month 24 | 1.5 percentage of participants |
Secondary
Percentage of Participants With Hyperphosphatemia
Hyperphosphatemia was defined as a phosphate value of \> 2.1 mmol/L (6.5 mg/dL) in one measurement. Serum phosphate was measured at every study visit.
Time frame: Baseline and Months 3, 6, 12, 18, and 24
Population: Intent-to-treat; LOCF was used. n indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol IV | Percentage of Participants With Hyperphosphatemia | Baseline (n=65) | 0.0 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hyperphosphatemia | Month 3 (n=67) | 28.4 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hyperphosphatemia | Month 6 (n=67) | 31.3 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hyperphosphatemia | Month 12 (n=67) | 25.4 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hyperphosphatemia | Month 18 (n=67) | 23.9 percentage of participants |
| Paricalcitol IV | Percentage of Participants With Hyperphosphatemia | Month 24 (n=67) | 22.4 percentage of participants |