Hyperparathyroidism, Secondary, Renal Disease, End Stage, Transplant; Failure, Kidney
Conditions
Keywords
Paricalcitol, Parathyroid Hormone, Bone Alkaline Phosphatase, Chronic Kidney Disease, Glomerular Filtration Rate, Vitamin D Receptor, Interstitial Fibrosis and Tubular Atrophy, Zemplar®
Brief summary
This study is being done to find out whether patients who receive a kidney transplant can benefit from taking the medication paricalcitol (trade name Zemplar®) as compared to kidney transplant recipients not taking this medication. The main possible benefits being studied are: * Lower risk for overactive parathyroid glands after kidney transplantation. * Lower risk of low bone density in the spine and hip after kidney transplantation. By dividing patients in the study into a group receiving Zemplar® and a group not receiving Zemplar®, it will be possible to understand the good and bad effects of Zemplar® during the first year after a kidney transplant.
Detailed description
The most significant challenge in kidney transplantation at present is that of reducing the risk of long-term complications. This includes hyperparathyroidism, a common post kidney transplant complication that contributes to loss of bone density and fracture risk and necessitates surgical intervention in approximately 5% of kidney transplant patients. In order to take part in the study you will already have been accepted for kidney transplantation from a living donor or from a deceased donor at Mayo Clinic in Rochester, Minnesota. After you have agreed to take part in the study you will be put in one of two groups by chance (as in the flip of a coin): Group 1 (Standard Treatment or Control): Patients in this group will receive a combination of four anti-rejection medications that have been used at Mayo Clinic Rochester for many kidney transplant patients and does not include any research study medicines. These medications will include: 1. Alemtuzumab (Campath®) - this medicine will be given intravenously (IV) on the day of the transplant during surgery. 2. Methylprednisolone (Solumedrol®) - this medicine, which is part of a family of medicines often referred to as corticosteroids, will be given intravenously on the day of the transplant during surgery. This will be the only planned dose of corticosteroid medicine you will receive although this medicine and a tablet form called Prednisone may be given at a later time if you have an episode of transplant rejection. 3. Mycophenolate Mofetil (Cellcept®) - this medicine will be given by mouth twice daily beginning the evening before the transplant (for living donor transplants) or the day of the transplant (for deceased donor transplants). It will be continued for as long as you have your transplant unless there is a medical reason to stop it. 4. Tacrolimus (Prograf®) - this medicine will be given by mouth once daily beginning on the fourth day after the transplant. It will continue for as long as you have your transplant unless there is a medical reason to stop it. The dose will be adjusted based on a blood test that will be done between twice a week and once a month for as long as you take the medicine. Group 2 (Zemplar® + Standard Treatment): Patients in this group will receive the same combination of anti-rejection medications as the patients in Group 1 (a-d above) plus Zemplar®, which is the medicine being studied, will also be started on the day of the transplant. Zemplar® will be given as a capsule containing 1 microgram of Zemplar® once daily beginning the day after the transplant. It will be continued at the same dose for the first two weeks then, depending on the results of blood and urine testing, will be increased to 2 micrograms daily. The dose will remain at 2 micrograms daily until the end of the study unless there is a medical reason to reduce or stop it or unless the study is stopped early. Both groups of patients will be treated by the same team of doctors, nurses and nurse coordinators that care for all kidney transplant patients at Mayo Clinic. The procedures and treatments for your transplant will be the same as those recommended at Mayo Clinic for all patients receiving a kidney transplant. These include the surgical operation to carry out the transplant; the need to take anti-rejection medicines by mouth for the rest of your life; the need to have blood and urine testing at regular intervals for the rest of your life to monitor the progress of your transplant; and the recommendation to have a biopsy of your transplant carried out on three occasion during the first two years after the transplant surgery. These procedures and their potential complications will be described to you in detail by your transplant physician, transplant surgeon, and transplant coordinator. The study will not require extra hospital or outpatient visits compared to the usual care for all kidney transplant patients at Mayo Clinic Rochester.
Interventions
DRUGParicalcitol
Zemplar® - this medicine, which is the medicine being studied, will be given as a capsule containing 1 microgram of Zemplar® once daily beginning the day after the transplant. It will be continued at the same dose for the first two weeks then, depending on the results of blood and urine testing, will be increased to 2 micrograms daily. The dose will remain at 2 micrograms daily until the end of the study unless there is a medical reason to reduce or stop it or unless the study is stopped early.
OTHERCorticosteroid Avoidance Immune Suppression Protocol
Induction with Alemtuzumab and maintenance with Tacrolimus and Mycophenolate Mofetil. With standard antimicrobial prophylaxis and calcium supplementation.
Sponsors
Abbott
Mayo Clinic
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
* Age 18 years and older. * First or second deceased donor or living donor renal transplant. * Normocalcemia or hypocalcemia. * Willing to give informed consent
Exclusion criteria
* Third or subsequent renal transplant. * Incompatible blood type or positive cross-match donor. * Multiple organ transplant recipients. * Diabetic with plans for future pancreas or islet transplant. * Evidence of donor-specific sensitization (positive T-cell and/or B-cell flow cytometric cross-match). * Documented hypercalcemia (total serum calcium 10.5 mg/dl on two separate occasions) prior to transplantation. * Serum 25(OH)vitamin D concentration ≤ 10 ng/ml
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Hyperparathyroidism at One Year | 1 year post kidney transplant | Parathyroid hormone (PTH) is a measure of how well the parathyroid gland is working and is measured by a blood test. Hyperparathyroidism (increased PTH) is defined as PTH blood value greater than 65 picograms/milliliter in the absence of hypocalcemia (low calcium) or if the subject had a parathyroidectomy (surgical removal of parathyroid glands) during the first year post-transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Osteopenia/Osteoporosis of the Lumbar Spine at One Year | 1 year post kidney transplant | Osteopenia/Osteoporosis are conditions where bone mineral density is lower than normal, reported by T-scores, measurements of the lower spine made using an Dual Energy X-ray Absorptiometry (DEXA) scan. The T-score is measured and compared to a normal healthy adult. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Each participant will be categorized as having or not having osteopenia/osteoporosis of the lumbar spine at the end of the first post-transplant year based on bone mineral density results. |
| Serum Parathyroid Hormone (PTH) Level Over Time | Baseline, 3 weeks, 3 months, 1 year post kidney transplant | Parathyroid hormone (PTH) is a hormone synthesized in the body's parathyroid glands that controls bone health. PTH controls calcium and phosphorus levels in the body. It is measured in the serum and reported in picograms per milliliter (pg/mL). |
| Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Baseline, 21 days, 90 days and 1 year post kidney transplant | BAP is a marker of bone turn-over, is measured in the serum and reported in micrograms per liter (mcg/L). |
| Change in Lumbar Spine Bone Mineral Density (BMD) | Baseline, 1 year post kidney transplant | BMD was measured using a Dual Energy X-ray Absorptiometry (DEXA) scan and reported by T-scores, measurements of the lower spine made using the scan. The T-score reflects how your bone density measurement compares to normal healthy adults. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Osteopenia is a condition of decreased bone mass or density but not thin enough to be diagnosed as osteoporosis. Osteoporosis is a condition where bone mass/density has diminished to a level causing higher risk of fracture. The average change in T-score from baseline to one year is reported. |
| Change in Hip Bone Mineral Density (BMD) | Baseline, 1 year post kidney transplant | BMD was measured using a Dual Energy X-ray Absorptiometry (DEXA) scan and reported by T-scores, measurements made of the hip bones using the scan. The T-score reflects how your bone density measurement compares to normal healthy adults. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Osteopenia is a condition of decreased bone mass or density but not thin enough to be diagnosed as osteoporosis. Osteoporosis is a condition where bone mass/density has diminished to a level causing higher risk of fracture. The average change in T-score from baseline to one year is reported. |
| Number of Subjects With Osteopenia/Osteoporosis of the Hip at One Year | 1 year post kidney transplant | Osteopenia/Osteoporosis are conditions where bone mineral density is lower than normal, reported by T-scores, measurements of the hip made using an Dual Energy X-ray Absorptiometry (DEXA) scan. The T-score is measured and compared to a normal healthy adult. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Each participant will be categorized as having or not having osteopenia/osteoporosis of the hip at the end of the first post-transplant year based on bone mineral density results. |
| Episodes of Acute Cellular Rejection (ACR) of the Renal Transplant | Baseline to 1 year post kidney transplant | The number of episodes of ACR, as proven by renal biopsy, were recorded. |
| Mean Estimated Glomerular Filtration Rate (eGFR) at One Year | 1 year post kidney transplant | Glomerular filtration rate describes the amount that fluid is filtered through the kidney and can be estimated by using serum creatinine. eGFR is reported in milliliters per minute per 1.73 m\^2 of body-surface area. |
| Mean Change in Estimated Glomerular Filtration Rate (eGFR) Between 3 Weeks and 1 Year Post Transplant | 3 weeks, 1 year post kidney transplant | — |
| 24-hour Total Protein in the Urine at 1 Year Post Transplant | 1 year post kidney transplant | A urine total protein test is conducted to detect excess protein in the urine. This test helps determine an individual's kidney functioning. Protein is not usually present in urine; therefore, presence of protein in the urine is a sign of abnormality. The quantity of protein in a sample of urine collected over 24-hour was measured and reported in milligrams per day. |
| Degree of Interstitial Fibrosis on Graft Biopsy at One Year | 1 year post kidney transplant | Interstitial fibrosis refers to degree of scarring or fibrous tissue formed in the kidney. Renal pathologists reviewed biopsies of the subject's kidney grafts for fibrosis, with results expressed using the Banff schema; Quantitative criteria: ci0 = fibrosis observed in up to 5% of cortical area, ci1 = fibrosis in 6%-25% of cortical area (mild) , ci2 = fibrosis in 26%-50% of cortical area (moderate), ci3 = fibrosis in greater than 50% of cortical area (severe). The degree of interstital fibrosis for this study was defined and reported as follows: a Banff ci score of greater than 0 and less than 2 considered mild fibrosis and a ci score greater than or equal to 2 as moderate to severe fibrosis. |
| Number of Subjects Who Died or Lost Their Renal Graft During First Year | Baseline to 1 year post kidney transplant | The number of subject who died (or experienced failure of their kidney surgical graft) during the first year following kidney transplant are reported here. |
Countries
United States
Participant flow
Recruitment details
Patients to undergo kidney transplantation at Mayo Clinic facilities in Rochester, Minnesota and in Scottsdale, Arizona and scheduled to receive corticosteroid avoidance anti-rejection therapy were screened for enrollment into the study.
Pre-assignment details
112 patients were approached for enrollment. Of those, 4 patient's treating physicians did not think corticosteroid free immunosuppression was appropriate, 3 had their transplants cancelled, 3 were found to be vitamin D deficient, 1 withdrew consent prior to randomization & 1 had a positive final crossmatch and hence were excluded from the study.
Participants by arm
| Arm | Count |
|---|---|
| Immunosuppression Without Paricalcitol (Control) Subjects will receive the standard immunosuppressive therapies of Alemtuzumab (Campath®), Methylprednisolone (Solumedrol®), Mycophenolate Mofetil (Cellcept®) and Tacrolimus (Prograf®). | 49 |
| Immunosuppression With Paricalcitol Subjects will receive the standard immunosuppressive medications; Alemtuzumab (Campath®), Methylprednisolone (Solumedrol®),Mycophenolate Mofetil (Cellcept®) and Tacrolimus (Prograf®), and in addition will receive the study medication paricalcitol (Zemplar®). | 51 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Did not want to do 24 hr urine collect. | 4 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Subject did not want to take study med | 0 | 1 |
Baseline characteristics
| Characteristic | Immunosuppression With Paricalcitol | Immunosuppression Without Paricalcitol (Control) | Total |
|---|---|---|---|
| Age Continuous | 48.5 years STANDARD_DEVIATION 10.3 | 47.7 years STANDARD_DEVIATION 10 | 48.1 years STANDARD_DEVIATION 10.1 |
| Cause of End-Stage Renal Disease Adult Polycystic Kidney Disease | 16 participants | 14 participants | 30 participants |
| Cause of End-Stage Renal Disease Diabetic | 8 participants | 10 participants | 18 participants |
| Cause of End-Stage Renal Disease Glomerulonephritis | 16 participants | 17 participants | 33 participants |
| Cause of End-Stage Renal Disease Hypertension | 3 participants | 1 participants | 4 participants |
| Cause of End-Stage Renal Disease Other | 8 participants | 7 participants | 15 participants |
| Degree of interstitial fibrosis Mild fibrosis at baseline | 3 Participants | 2 Participants | 5 Participants |
| Degree of interstitial fibrosis Moderate to severe fibrosis at baseline | 0 Participants | 0 Participants | 0 Participants |
| Diabetes | 10 participants | 12 participants | 22 participants |
| First transplant | 50 participants | 47 participants | 97 participants |
| Living kidney donor | 48 participants | 48 participants | 96 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 49 Participants | 42 Participants | 91 Participants |
| Region of Enrollment United States | 51 participants | 49 participants | 100 participants |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 34 Participants |
| Sex: Female, Male Male | 33 Participants | 33 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 49 | 32 / 51 |
| serious Total, serious adverse events | 16 / 49 | 27 / 51 |
Outcome results
Primary
Number of Subjects With Hyperparathyroidism at One Year
Parathyroid hormone (PTH) is a measure of how well the parathyroid gland is working and is measured by a blood test. Hyperparathyroidism (increased PTH) is defined as PTH blood value greater than 65 picograms/milliliter in the absence of hypocalcemia (low calcium) or if the subject had a parathyroidectomy (surgical removal of parathyroid glands) during the first year post-transplant.
Time frame: 1 year post kidney transplant
Population: Analysis was performed by the intention-to-treat principle, comprised of all subjects enrolled, who will have taken at least one dose of study medication and have both screening and any post-screening efficacy data recorded. The last observation was carried forward for missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Number of Subjects With Hyperparathyroidism at One Year | 31 Participants |
| Immunosuppression With Paricalcitol | Number of Subjects With Hyperparathyroidism at One Year | 15 Participants |
p-value: 0.0005Fisher Exact
Secondary
24-hour Total Protein in the Urine at 1 Year Post Transplant
A urine total protein test is conducted to detect excess protein in the urine. This test helps determine an individual's kidney functioning. Protein is not usually present in urine; therefore, presence of protein in the urine is a sign of abnormality. The quantity of protein in a sample of urine collected over 24-hour was measured and reported in milligrams per day.
Time frame: 1 year post kidney transplant
Population: Per-protocol analysis. The 24-hour urine collection was not completed for all subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | 24-hour Total Protein in the Urine at 1 Year Post Transplant | 420.8 mg/day | Standard Deviation 1052.3 |
| Immunosuppression With Paricalcitol | 24-hour Total Protein in the Urine at 1 Year Post Transplant | 159.4 mg/day | Standard Deviation 235.8 |
p-value: 0.11t-test, 2 sided
Secondary
Change in Hip Bone Mineral Density (BMD)
BMD was measured using a Dual Energy X-ray Absorptiometry (DEXA) scan and reported by T-scores, measurements made of the hip bones using the scan. The T-score reflects how your bone density measurement compares to normal healthy adults. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Osteopenia is a condition of decreased bone mass or density but not thin enough to be diagnosed as osteoporosis. Osteoporosis is a condition where bone mass/density has diminished to a level causing higher risk of fracture. The average change in T-score from baseline to one year is reported.
Time frame: Baseline, 1 year post kidney transplant
Population: Per-protocol analysis. Not all subjects were able to undergo the DEXA scan of the hip at baseline and one-year \[Control n = 41/Treatment n = 40\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Change in Hip Bone Mineral Density (BMD) | 0.15 T-score | Standard Deviation 0.27 |
| Immunosuppression With Paricalcitol | Change in Hip Bone Mineral Density (BMD) | 0.21 T-score | Standard Deviation 0.36 |
p-value: 0.41t-test, 2 sided
Secondary
Change in Lumbar Spine Bone Mineral Density (BMD)
BMD was measured using a Dual Energy X-ray Absorptiometry (DEXA) scan and reported by T-scores, measurements of the lower spine made using the scan. The T-score reflects how your bone density measurement compares to normal healthy adults. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Osteopenia is a condition of decreased bone mass or density but not thin enough to be diagnosed as osteoporosis. Osteoporosis is a condition where bone mass/density has diminished to a level causing higher risk of fracture. The average change in T-score from baseline to one year is reported.
Time frame: Baseline, 1 year post kidney transplant
Population: Per-protocol analysis; Not all subjects were able to undergo the DEXA scan of the spine at baseline and one-year \[Control n = 42/Treatment n = 41\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Change in Lumbar Spine Bone Mineral Density (BMD) | 0.35 T-score | Standard Deviation 0.45 |
| Immunosuppression With Paricalcitol | Change in Lumbar Spine Bone Mineral Density (BMD) | 0.35 T-score | Standard Deviation 0.58 |
p-value: 0.98t-test, 2 sided
Secondary
Degree of Interstitial Fibrosis on Graft Biopsy at One Year
Interstitial fibrosis refers to degree of scarring or fibrous tissue formed in the kidney. Renal pathologists reviewed biopsies of the subject's kidney grafts for fibrosis, with results expressed using the Banff schema; Quantitative criteria: ci0 = fibrosis observed in up to 5% of cortical area, ci1 = fibrosis in 6%-25% of cortical area (mild) , ci2 = fibrosis in 26%-50% of cortical area (moderate), ci3 = fibrosis in greater than 50% of cortical area (severe). The degree of interstital fibrosis for this study was defined and reported as follows: a Banff ci score of greater than 0 and less than 2 considered mild fibrosis and a ci score greater than or equal to 2 as moderate to severe fibrosis.
Time frame: 1 year post kidney transplant
Population: Per-protocol analysis; graft biopsies were not available for all subjects
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Degree of Interstitial Fibrosis on Graft Biopsy at One Year | Mild fibrosis at 1 year | 19 Participants | 50 |
| Immunosuppression Without Paricalcitol (Control) | Degree of Interstitial Fibrosis on Graft Biopsy at One Year | Moderate to severe fibrosis at 1 year | 4 Participants | 10.5 |
| Immunosuppression With Paricalcitol | Degree of Interstitial Fibrosis on Graft Biopsy at One Year | Mild fibrosis at 1 year | 19 Participants | 50 |
| Immunosuppression With Paricalcitol | Degree of Interstitial Fibrosis on Graft Biopsy at One Year | Moderate to severe fibrosis at 1 year | 0 Participants | 0 |
Comparison: The number of subjects with mild interstitial fibrosis (Banff ci score \> 0 and \< 2) at one year was compared between treatment groups.p-value: 1t-test, 2 sided
Comparison: The number of subjects with moderate to mild interstitial fibrosis (Banff ci score greater than or equal to 2) at one year was compared between treatment groups.p-value: 0.04t-test, 2 sided
Secondary
Episodes of Acute Cellular Rejection (ACR) of the Renal Transplant
The number of episodes of ACR, as proven by renal biopsy, were recorded.
Time frame: Baseline to 1 year post kidney transplant
Population: Per-protocol analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Episodes of Acute Cellular Rejection (ACR) of the Renal Transplant | 5 episodes |
| Immunosuppression With Paricalcitol | Episodes of Acute Cellular Rejection (ACR) of the Renal Transplant | 4 episodes |
Secondary
Mean Change in Estimated Glomerular Filtration Rate (eGFR) Between 3 Weeks and 1 Year Post Transplant
Time frame: 3 weeks, 1 year post kidney transplant
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Mean Change in Estimated Glomerular Filtration Rate (eGFR) Between 3 Weeks and 1 Year Post Transplant | 7.4 mL/min/1.73 m^2 | Standard Deviation 15.1 |
| Immunosuppression With Paricalcitol | Mean Change in Estimated Glomerular Filtration Rate (eGFR) Between 3 Weeks and 1 Year Post Transplant | 6.2 mL/min/1.73 m^2 | Standard Deviation 10.4 |
p-value: 0.66t-test, 2 sided
Secondary
Mean Estimated Glomerular Filtration Rate (eGFR) at One Year
Glomerular filtration rate describes the amount that fluid is filtered through the kidney and can be estimated by using serum creatinine. eGFR is reported in milliliters per minute per 1.73 m\^2 of body-surface area.
Time frame: 1 year post kidney transplant
Population: Per-protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Mean Estimated Glomerular Filtration Rate (eGFR) at One Year | 52.7 mL/min/1.73m^2 | Standard Deviation 14.1 |
| Immunosuppression With Paricalcitol | Mean Estimated Glomerular Filtration Rate (eGFR) at One Year | 51.2 mL/min/1.73m^2 | Standard Deviation 15.4 |
p-value: 0.66t-test, 2 sided
Secondary
Number of Subjects Who Died or Lost Their Renal Graft During First Year
The number of subject who died (or experienced failure of their kidney surgical graft) during the first year following kidney transplant are reported here.
Time frame: Baseline to 1 year post kidney transplant
Population: Per-protocol analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Number of Subjects Who Died or Lost Their Renal Graft During First Year | 0 participants |
| Immunosuppression With Paricalcitol | Number of Subjects Who Died or Lost Their Renal Graft During First Year | 1 participants |
Secondary
Number of Subjects With Osteopenia/Osteoporosis of the Hip at One Year
Osteopenia/Osteoporosis are conditions where bone mineral density is lower than normal, reported by T-scores, measurements of the hip made using an Dual Energy X-ray Absorptiometry (DEXA) scan. The T-score is measured and compared to a normal healthy adult. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Each participant will be categorized as having or not having osteopenia/osteoporosis of the hip at the end of the first post-transplant year based on bone mineral density results.
Time frame: 1 year post kidney transplant
Population: Per-protocol analysis. Data were not available for 2 control subjects and 2 treatment subjects, as these subjects did not have the DEXA scan of the hip done at one year. \[Control n=42/ Treatment=41\]
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Number of Subjects With Osteopenia/Osteoporosis of the Hip at One Year | 9 Participants |
| Immunosuppression With Paricalcitol | Number of Subjects With Osteopenia/Osteoporosis of the Hip at One Year | 12 Participants |
p-value: 0.4571Fisher Exact
Secondary
Number of Subjects With Osteopenia/Osteoporosis of the Lumbar Spine at One Year
Osteopenia/Osteoporosis are conditions where bone mineral density is lower than normal, reported by T-scores, measurements of the lower spine made using an Dual Energy X-ray Absorptiometry (DEXA) scan. The T-score is measured and compared to a normal healthy adult. A normal bone density results in a T-score between +1.0 and -1.0. A T-score of less than or equal to -1.5 was used for this study to define the presence of osteopenia/osteoporosis. Each participant will be categorized as having or not having osteopenia/osteoporosis of the lumbar spine at the end of the first post-transplant year based on bone mineral density results.
Time frame: 1 year post kidney transplant
Population: Per-protocol analysis; Data were not available for 1 subject from each arm because these subjects did not have the one year DEXA scan of the spine. \[Control n = 43/Treatment n = 42\].
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Number of Subjects With Osteopenia/Osteoporosis of the Lumbar Spine at One Year | 9 Participants |
| Immunosuppression With Paricalcitol | Number of Subjects With Osteopenia/Osteoporosis of the Lumbar Spine at One Year | 14 Participants |
p-value: 0.229Fisher Exact
Secondary
Serum Bone Alkaline Phosphatase (BAP) Level Over Time
BAP is a marker of bone turn-over, is measured in the serum and reported in micrograms per liter (mcg/L).
Time frame: Baseline, 21 days, 90 days and 1 year post kidney transplant
Population: Per-protocol analysis; the number of samples obtained at each time point varied because not all subjects were able to undergo laboratory testing at the specified study visits. The number of subjects samples per treatment group were as follows \[Timepoint: Control(n)/Treatment(n)\]:~Baseline: 43/41, Day 21: 34/38, Day 90: 36/36, Day 365: 43/41
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Baseline BAP | 14 mcg/L |
| Immunosuppression Without Paricalcitol (Control) | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Day 21 BAP | 16.5 mcg/L |
| Immunosuppression Without Paricalcitol (Control) | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Day 90 BAP | 21 mcg/L |
| Immunosuppression Without Paricalcitol (Control) | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Day 365 BAP | 14 mcg/L |
| Immunosuppression With Paricalcitol | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Day 365 BAP | 11 mcg/L |
| Immunosuppression With Paricalcitol | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Baseline BAP | 13 mcg/L |
| Immunosuppression With Paricalcitol | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Day 90 BAP | 12 mcg/L |
| Immunosuppression With Paricalcitol | Serum Bone Alkaline Phosphatase (BAP) Level Over Time | Day 21 BAP | 17 mcg/L |
Comparison: The median BAP level at baseline was compared between the two treatment groups.p-value: 0.833Wilcoxon (Mann-Whitney)
Comparison: The median BAP level at 21 days was compared between the two treatment groups.p-value: 0.553Wilcoxon (Mann-Whitney)
Comparison: The median BAP level at 90 days was compared between the two treatment groups.p-value: 0.035Wilcoxon (Mann-Whitney)
Comparison: The median BAP level at one year was compared between the two treatment groups.p-value: 0.171Wilcoxon (Mann-Whitney)
Secondary
Serum Parathyroid Hormone (PTH) Level Over Time
Parathyroid hormone (PTH) is a hormone synthesized in the body's parathyroid glands that controls bone health. PTH controls calcium and phosphorus levels in the body. It is measured in the serum and reported in picograms per milliliter (pg/mL).
Time frame: Baseline, 3 weeks, 3 months, 1 year post kidney transplant
Population: Per-protocol analysis; the number of samples obtained at each time point varied because not all subjects were able to undergo laboratory testing at the specified timepoints. The number of subjects samples per treatment group were as follows \[Timepoint: Control(n)/Treatment(n)\]:~Baseline: 43/41, Day 21: 44/41, Day 90: 44/43, Day 365: 44/43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Immunosuppression Without Paricalcitol (Control) | Serum Parathyroid Hormone (PTH) Level Over Time | 21 day PTH level | 69 pg/mL |
| Immunosuppression Without Paricalcitol (Control) | Serum Parathyroid Hormone (PTH) Level Over Time | Baseline PTH level | 236 pg/mL |
| Immunosuppression Without Paricalcitol (Control) | Serum Parathyroid Hormone (PTH) Level Over Time | 3 month PTH level | 70 pg/mL |
| Immunosuppression Without Paricalcitol (Control) | Serum Parathyroid Hormone (PTH) Level Over Time | 1 year PTH level | 85 pg/mL |
| Immunosuppression With Paricalcitol | Serum Parathyroid Hormone (PTH) Level Over Time | 1 year PTH level | 42 pg/mL |
| Immunosuppression With Paricalcitol | Serum Parathyroid Hormone (PTH) Level Over Time | 3 month PTH level | 42 pg/mL |
| Immunosuppression With Paricalcitol | Serum Parathyroid Hormone (PTH) Level Over Time | Baseline PTH level | 198 pg/mL |
| Immunosuppression With Paricalcitol | Serum Parathyroid Hormone (PTH) Level Over Time | 21 day PTH level | 50 pg/mL |
Comparison: The median PTH level at baseline was compared between the two treatment groups.p-value: 0.17Wilcoxon (Mann-Whitney)
Comparison: The median PTH level at 21 days was compared between the two treatment groups.p-value: 0.005Wilcoxon (Mann-Whitney)
Comparison: The median PTH level at 90 days was compared between the two treatment groups.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: The median PTH level at one year was compared between the two treatment groups.p-value: 0.0004Wilcoxon (Mann-Whitney)