Chronic Kidney Disease, Secondary Hyperparathyroidism
Conditions
Keywords
Secondary hyperparathyroidism, Mineral and Bone Disorder (CKD-MBD), Chronic Kidney Disease
Brief summary
Paricalcitol capsules (Zemplar®) received marketing authorization in Sweden in late 2007 for the prevention and treatment of secondary hyperparathyroidism in patients with Stage 3 & 4 Chronic Kidney Disease (CKD). Accordingly, additional data is needed to evaluate the effectiveness and safety of paricalcitol therapy under conditions of usual clinical care in Sweden. This observational study is designed to collect data to evaluate safety and effectiveness during 6 months of therapy with paricalcitol capsules prescribed for patients with CKD Stages 3-5 not yet on dialysis. Data will also be collected on patient quality of life and costs associated with patient care.
Detailed description
This observational study is designed to collect data to evaluate safety and effectiveness during 6 months of therapy with paricalcitol capsules prescribed in accordance with the terms of the marketing authorization for patients with Chronic Kidney Disease (CKD) Stages 3-5 not yet on dialysis. Data will also be collected on patient quality of life and costs associated with patient care. A retrospective chart review of patient laboratory and medication history will provide historical data to determine drivers for initiation of paricalcitol therapy. The primary goal of this post-marketing observational study (PMOS) is to further characterize the prescribing habits and patient management practices of physicians prescribing paricalcitol capsules and to assess the metabolic safety and effectiveness of paricalcitol capsules for the treatment of secondary hyperparathyroidism in Stage 3-5 CKD patients not yet on dialysis under conditions of usual clinical care. Focus will be to examine the practice of dose titration in early stages of CKD, understand real-world management of intact parathyroid hormone levels, understand real-world incidence and management of abnormalities in serum calcium and phosphate, and to examine patient bone and mineral profiles and medical history to understand drivers for paricalcitol capsules use. Patients prescribed paricalcitol therapy for the first time will be asked to participate in the study. Enrolled patients will be followed for 6 months.
Interventions
None listed
Sponsors
Pharma Consulting Group AB
AbbVie (prior sponsor, Abbott)
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must sign the Informed Consent Form prior to inclusion into the study * Patients should satisfy the Swedish Summary of Product Characteristics (SPC) for paricalcitol capsules at www.fass.se * Patients must be 18 years or older with a diagnosis of secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD) Stages 3 - 5 (estimated Glomerular Filtration Rate between 10-59 by Modification of Diet in Renal Disease) but not yet on dialysis * Patients should be in stable condition and have a life expectancy of at least 6 months * Patients should not be expected to be transplanted or initiate dialysis for at least 6 months
Exclusion criteria
* Patients with CKD receiving dialysis * Patients contraindicated for paricalcitol capsules as described in the SPC * Treatment with paricalcitol more than 20 days prior to study enrollment * History of drug or alcohol abuse within 6 months prior to inclusion * History of non-compliance with medication or a medical history (i.e. psychiatric) that could enhance non-compliance with medication as determined by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Intact Parathyroid Hormone at 6 Months | Baseline and 6 months | — |
| Percentage of Participants With Intact Parathyroid Hormone Within K/DOQI Target Range at Baseline and 6 Months | Baseline and 6 months | Kidney Disease Outcomes Quality Initiative (K/DOQI) target intact parathyroid hormone (iPTH) levels are: Stage 3 CKD (estimated Glomerular Filtration Rate\* \[eGFR\] 30 - 59 mL/min): 3.85 - 7.7 pmol/L; Stage 4 CKD (eGFR 15 - 29 mL/min): 7.7 - 12.1 pmol/L; Stage 5 CKD (eGFR \< 15 mL/min): 16.5 - 33 pmol/L. \*Calculated using the Modification of Diet in Renal Disease formula. |
| Percentage of Participants With Elevated Serum-Phosphorus (s-P) Levels at Baseline and 6 Months | Baseline and 6 months | Elevated serum phosphorus is defined according to the 2003 Kidney Disease Outcomes Quality Initiative (K/DOQI) target definitions as: Stage 3 CKD: ≥ 1.49 mmol/L; Stage 4 CKD: ≥ 1.49 mmol/L; Stage 5 CKD: \> 1.78 mmol/L. |
| Percentage of Participants With Elevated Serum-Calcium (s-Ca) Levels at Baseline and 6 Months | Baseline and 6 months | Elevated serum calcium is defined according to the 2003 Kidney Disease Outcomes Quality Initiative (K/DOQI) target definitions of s-Ca above 2.37 mmol/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Indirect Costs of Care Associated With Secondary Hyperparathyroidism | 6 months | Indirect costs were estimated by using the number of hours missed from work (absenteeism) multiplied by the average hourly labor cost, including wages and benefits, to calculate average lost productivity costs due to absenteeism during the preceding 7 days. Hours missed from work were assessed using the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI-GH) questionnaire, in which respondents answer 6 questions related to work productivity and impairment. Unit costs were taken from official sources (Statistics Sweden, www.scb.se) and published literature. |
| Change From Baseline in Proteinuria | Baseline and Month 6 | Proteinuria is the presence of excess serum proteins, or albumin, in the urine. Proteinuria was measured by the amount of albumin per liter of urine. |
| Number of Participants Using Concomitant Medications at Baseline | Baseline | — |
| Percentage of Participants With a Reduction of Proteinuria of at Least 15% From Baseline | Baseline and 6 months | — |
| Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | Baseline and 6 months | The KDQOL-SF is a self-report measure developed for individuals with kidney disease. It includes 43 end-stage renal disease (ESRD)-targeted items focused on particular areas of concern for individuals with kidney disease (Symptoms/problems, Effects of the disease on daily life, Burden of disease, Work status, Cognitive function, Quality of social interaction, Sexual function, Sleep, and Social support), 36 items (SF-36) that provide 8 measures of physical and mental health (Physical functioning, Role limitations caused by physical health limitations, Role limitations caused by emotional health problems, Social functioning, Emotional well-being, Pain, Energy/fatigue and General health perceptions), and 1 overall health rating item where respondents rate their health on a scale from 0 (worst possible health) to 10 (best possible health). Scores are transformed and calculated such that each scale score ranges from 0 to 100 where higher scores reflect a better quality of life. |
| Total Direct Costs of Care Associated With Secondary Hyperparathyroidism | 6 months | Direct medical costs to be calculated included outpatient visits, hospitalizations, pharmaceuticals, etc. However the data collected in this observational study was not enough to support this calculation. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paricalcitol Capsules Patients with secondary hyperparathyroidism associated with Stage 3 - 5 CKD and not yet on dialysis and prescribed paricalcitol capsules in accordance with the terms of the marketing authorization in Sweden. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reasons | 2 |
| Overall Study | Adverse Event | 1 |
| Overall Study | Did not receive treatment | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Stopped treatment | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Paricalcitol Capsules |
|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized American (Indian/Alaska Native) | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black | 0 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White | 49 participants |
| Region of Enrollment Sweden | 49 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 12 / 49 |
Outcome results
Primary
Change From Baseline in Intact Parathyroid Hormone at 6 Months
Time frame: Baseline and 6 months
Population: Per-Protocol Analysis Set (PPAS), defined as all included participants who received at least 1 dose of paricalcitol capsules and had analyzable data for the primary endpoints, i.e., 5 - 8 months after inclusion, and with available iPTH data at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol Capsules | Change From Baseline in Intact Parathyroid Hormone at 6 Months | -6.2 pmol/L | Standard Deviation 13 |
Primary
Percentage of Participants With Elevated Serum-Calcium (s-Ca) Levels at Baseline and 6 Months
Elevated serum calcium is defined according to the 2003 Kidney Disease Outcomes Quality Initiative (K/DOQI) target definitions of s-Ca above 2.37 mmol/L.
Time frame: Baseline and 6 months
Population: Per-protocol analysis set. One participant had missing s-Ca data at Baseline and one participant had missing s-Ca data at month 6; percentages are based on the total number of participants in the per-protocol analysis set (40).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol Capsules | Percentage of Participants With Elevated Serum-Calcium (s-Ca) Levels at Baseline and 6 Months | Baseline | 42.5 percentage of participants |
| Paricalcitol Capsules | Percentage of Participants With Elevated Serum-Calcium (s-Ca) Levels at Baseline and 6 Months | 6 months | 42.5 percentage of participants |
Primary
Percentage of Participants With Elevated Serum-Phosphorus (s-P) Levels at Baseline and 6 Months
Elevated serum phosphorus is defined according to the 2003 Kidney Disease Outcomes Quality Initiative (K/DOQI) target definitions as: Stage 3 CKD: ≥ 1.49 mmol/L; Stage 4 CKD: ≥ 1.49 mmol/L; Stage 5 CKD: \> 1.78 mmol/L.
Time frame: Baseline and 6 months
Population: Per-protocol analysis set. Two patients had missing s-P data at month 6; percentages are based on the total number of participants in the per-protocol analysis set (40).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol Capsules | Percentage of Participants With Elevated Serum-Phosphorus (s-P) Levels at Baseline and 6 Months | Baseline | 15.0 percentage of participants |
| Paricalcitol Capsules | Percentage of Participants With Elevated Serum-Phosphorus (s-P) Levels at Baseline and 6 Months | 6 months | 25.0 percentage of participants |
Primary
Percentage of Participants With Intact Parathyroid Hormone Within K/DOQI Target Range at Baseline and 6 Months
Kidney Disease Outcomes Quality Initiative (K/DOQI) target intact parathyroid hormone (iPTH) levels are: Stage 3 CKD (estimated Glomerular Filtration Rate\* \[eGFR\] 30 - 59 mL/min): 3.85 - 7.7 pmol/L; Stage 4 CKD (eGFR 15 - 29 mL/min): 7.7 - 12.1 pmol/L; Stage 5 CKD (eGFR \< 15 mL/min): 16.5 - 33 pmol/L. \*Calculated using the Modification of Diet in Renal Disease formula.
Time frame: Baseline and 6 months
Population: Per-protocol analysis set. Three participants had missing data at Baseline and one participant had missing data at the 6 month visit; percentages are based on the total number of participants in the per-protocol analysis set (40).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol Capsules | Percentage of Participants With Intact Parathyroid Hormone Within K/DOQI Target Range at Baseline and 6 Months | Baseline | 15.0 percentage of participants |
| Paricalcitol Capsules | Percentage of Participants With Intact Parathyroid Hormone Within K/DOQI Target Range at Baseline and 6 Months | 6 months | 27.5 percentage of participants |
Secondary
Change From Baseline in Proteinuria
Proteinuria is the presence of excess serum proteins, or albumin, in the urine. Proteinuria was measured by the amount of albumin per liter of urine.
Time frame: Baseline and Month 6
Population: Per-protocol analysis set with available data at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol Capsules | Change From Baseline in Proteinuria | 0.2 g/L | Standard Deviation 0.7 |
Secondary
Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF)
The KDQOL-SF is a self-report measure developed for individuals with kidney disease. It includes 43 end-stage renal disease (ESRD)-targeted items focused on particular areas of concern for individuals with kidney disease (Symptoms/problems, Effects of the disease on daily life, Burden of disease, Work status, Cognitive function, Quality of social interaction, Sexual function, Sleep, and Social support), 36 items (SF-36) that provide 8 measures of physical and mental health (Physical functioning, Role limitations caused by physical health limitations, Role limitations caused by emotional health problems, Social functioning, Emotional well-being, Pain, Energy/fatigue and General health perceptions), and 1 overall health rating item where respondents rate their health on a scale from 0 (worst possible health) to 10 (best possible health). Scores are transformed and calculated such that each scale score ranges from 0 to 100 where higher scores reflect a better quality of life.
Time frame: Baseline and 6 months
Population: Per-protocol analysis set with available data at both time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Symptom/problem scale | -0.4 units on a scale | Standard Deviation 12.9 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Effects of kidney disease | -0.2 units on a scale | Standard Deviation 9.4 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Burden of kidney disease | -1.0 units on a scale | Standard Deviation 19.5 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Cognitive function | -2.5 units on a scale | Standard Deviation 19.7 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Sexual function | -0.6 units on a scale | Standard Deviation 23 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Social Support | -4.9 units on a scale | Standard Deviation 17.4 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Physical functioning | 5.7 units on a scale | Standard Deviation 18.6 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Role physical | -7.3 units on a scale | Standard Deviation 36.5 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Pain | -2.3 units on a scale | Standard Deviation 22.1 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: General health | 1.5 units on a scale | Standard Deviation 16.6 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Emotional well-being | -3.0 units on a scale | Standard Deviation 13.4 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Role emotional | -11.1 units on a scale | Standard Deviation 36.3 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | Overall health rating | 1.3 units on a scale | Standard Deviation 15.4 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Work status | -10.4 units on a scale | Standard Deviation 29.4 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Quality of social interaction | 1.7 units on a scale | Standard Deviation 20.3 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | ESRD: Sleep | 0.9 units on a scale | Standard Deviation 11.3 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Social function | 0.5 units on a scale | Standard Deviation 22 |
| Paricalcitol Capsules | Change From Baseline in Quality of Life Assessed by the Kidney Disease Quality of Life-Short Form (KDQOL-SF) | SF-36: Energy/fatigue | 1.9 units on a scale | Standard Deviation 22.4 |
Secondary
Number of Participants Using Concomitant Medications at Baseline
Time frame: Baseline
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Agents acting on the renin-angiotensin system | 39 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | All other therapeutic products | 11 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Angiotensin II antagonists, plain | 1 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Antianemic preparations | 10 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Antigout preparations | 9 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Antihypertensives | 5 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Antiprotozoals | 1 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Antithrombotic agents | 2 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Beta blocking agents | 22 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Blood substitutes and perfusion solutions | 10 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Calcium channel blockers | 27 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Calcium homeostasis | 1 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Cardiac therapy | 1 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Diuretics | 28 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Drugs for obstructive airway diseases | 1 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Drugs used in diabetes | 3 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Immunosuppressive agents | 1 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Lipid modifying agents | 28 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Mineral supplements | 10 participants |
| Paricalcitol Capsules | Number of Participants Using Concomitant Medications at Baseline | Vitamins | 2 participants |
Secondary
Percentage of Participants With a Reduction of Proteinuria of at Least 15% From Baseline
Time frame: Baseline and 6 months
Population: Per-protocol analysis set. Percentages are based on the total number of participants in the per-protocol analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paricalcitol Capsules | Percentage of Participants With a Reduction of Proteinuria of at Least 15% From Baseline | 10.0 percentage of participants |
Secondary
Total Direct Costs of Care Associated With Secondary Hyperparathyroidism
Direct medical costs to be calculated included outpatient visits, hospitalizations, pharmaceuticals, etc. However the data collected in this observational study was not enough to support this calculation.
Time frame: 6 months
Secondary
Total Indirect Costs of Care Associated With Secondary Hyperparathyroidism
Indirect costs were estimated by using the number of hours missed from work (absenteeism) multiplied by the average hourly labor cost, including wages and benefits, to calculate average lost productivity costs due to absenteeism during the preceding 7 days. Hours missed from work were assessed using the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI-GH) questionnaire, in which respondents answer 6 questions related to work productivity and impairment. Unit costs were taken from official sources (Statistics Sweden, www.scb.se) and published literature.
Time frame: 6 months
Population: Participants who were working for pay and with available data at both time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paricalcitol Capsules | Total Indirect Costs of Care Associated With Secondary Hyperparathyroidism | Absenteeism: Baseline | 0 Swedish krona per participant | Standard Deviation 0 |
| Paricalcitol Capsules | Total Indirect Costs of Care Associated With Secondary Hyperparathyroidism | Absenteeism: 6 months | 1,318 Swedish krona per participant | — |