Efficacy and Safety of Paricalcitol in the Reduction of Secondary Hyperparathyroidism After Kidney Transplantation.

Study Overview
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Brief Summary
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To demonstrate the superiority of paricalcitol treatment at early renal post-transplantation (M6) in the control of iPTH (Intact parathyroid hormone) compared to the use of vitamin D nutritional supplements (calcifediol) in patients with renal transplantation.

Detailed Description
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The purpose of this study is to demonstrate the superiority of paricalcitol treatment at early renal post-transplantation (M6) in the control of iPTH (Intact parathyroid hormone) compared to the use of vitamin D nutritional supplements (calcifediol) in patients with renal transplantation.

Official Title
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Efficacy and Safety of Paricalcitol in the Reduction of Secondary Hyperparathyroidism After Renal Transplantation.

Conditions
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Secondary Hyperparathyroidism Due to Renal Causes

Intervention / Treatment
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* Drug: Paricalcitol
* Drug: Calcifediol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient that have willingly signed and dated the ICD (Informed Consent Document) approved by the EC (Ethics Committee) before any study procedure and after they have been explained the study, they have read the ICD and have had the opportunity to make questions about it. Patients of both genders and older than 18 years candidates to an immediately renal transplantation from living or deceased donor. 24 hours previous to the transplantation, patient must have a significant grade of secondary hyperparathyroidism, defined as iPTH (Intact parathyroid hormone) levels between 110 and 600 pg/mL as per central laboratory results. Patients with a preformed antibody panel <20% 24 hours before the transplantation or that are considered by the investigator of low immunological risk (PRA determination is being done on local laboratory, not central). Serum calcium (corrected by albumin) < 10 mg/dL 24 hour previous to the transplantation as per central laboratory results. Patients that are to be treated with immunosuppression based on tacrolimus, mofetil mycofenolate or mycophenolic acid and with steroids and that are not going to be treated with mTOR (mammalian target of rapamycin) inhibitors. Tacrolimus and steroids must not be removed on the 6 month post-transplantation. Patients that are able to take oral capsules on the first week post-transplantation. Exclusion Criteria: Third or subsequent renal transplantation. Positive cross-match assay or ABO (A-B-0) incompatibility Patients that have been or are going to be recipients of other organs other than the kidney or a double kidney transplantation. Patients with history of allergic reaction or sensibility to paricalcitol, calcifediol or similar study drugs (related with vitamin D). Patients with chronic gastrointestinal disease, that, based on investigators criteria, can cause significant gastrointestinal malabsorption. Patient with hypo or hyperthyroidism not controlled based on investigators criteria. Patient with uncontrolled hypertension based on investigators criteria. Patients that, 48 hours previous to transplantation, have been receiving calcimimetics. Patients with VIH (human immunodeficiency virus)infection of positive serology for HBV (hepatitis B virus) and/or HCV (hepatitis C virus) Patients on treatment with drugs contraindicated with paricalcitol and calcifediol (based on SMPC) Patients that are participating on other clinical trial with investigational drugs. Women of childbearing potential (defined as those whose last menstruation was <2 years ago and that are not surgically sterilized) that are not willing to use correct contraception during study treatment. Patient with other diseases or conditions that based on investigators criteria are not suitable for the study. Treatment will not be started if the Calcium-Phosphorus product (CAxP)is >55 mg2/dL2 or in case of hyperphosphatemia considered significant as per investigator criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paricalcitol<br>Paricalcitol oral capsules. | Drug: Paricalcitol<br>* 1 capsule/day for 6 months. On Month 1 and Month 3 it can be increased up to 2 capsules/day or decreased down to 1 capsule/48 hours.<br>* Other names: Zemplar;|
| Active Comparator: Calcifediol<br>Calcifediol oral drops. | Drug: Calcifediol<br>* 5 drops/day during 6 months. On Month 1 it can be increased up to 7 drops/day. If this occurs then, on Month 3, it can decreased to 5 drops/day or continue 7 drops/day until end of treatment.<br>* Other names: Hidroferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With iPTH Serum Concentration >110 pg/mL. | Percentage of patients with iPTH serum concentration >110 pg/mL 6 month after transplant. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on iPTH Serum Concentration. Intention to Treat Analysis. | Change on iPTH serum concentration on each treatment group 6 month post transplantation. | 6 months | 
| Percentage of Patients That Reach at Least a 30% iPTH Reduction at the End of the Study. |  | 6 months | 
| Percentage of Patients With iPTH Levels Between 70-110 pg/mL at the End of the Study. ITT. |  | 6 month | 
| Percentage of Patient With Presence of Calcifications on Protocol Renal Biopsies at 6 Months After Treatment in Each Treatment Group. |  | 6 months | 
| Patients That Suffered the Following Events: Acute Rejection, Acute Rejection Confirmed With Biopsy and/or Subclinic Rejection and/or Chronic Damage. | Patients with at least one of the following events: acute rejection, acute rejection confirmed with biopsy and/or subclinic rejection and/or chronic damage. | 6 months | 
| Change on Concentration of Bone Markers (Osteocalcin) at 6 Months After Transplantation on Each Treatment Group. |  | 6 months | 
| Percentage of Patients With Acute Rejection at 6 Months After Transplantation and Treatment on Each Treatment Group. |  | 6 months | 
| Percentage of Patients With Microalbuminuria on Months 1, 3 and 6 Post Transplantation. |  | Months 1, 3 and 6 | 
| Percentage of Patients on Each Stage of Renal Function on Months 1, 3 and 6 Post Transplantation. |  | Months 1, 3 and 6 | 
| Evolution of Speed of Pulse Wave From Month 1 to Month 6 Post Transplantation. | Baseline speed of pulse wave was performed between 1 week and 1 month post transplant; next measure of speed of pulse wave performed at month 6 post transplant. | 6 months. | 
| Percentage of Patients With Hypercalcemia on Each Treatment Group at 6 Months Post Transplantation. | Percentage of patients with hypercalcemia (defined as serum calcium levels > 10,3 mg/dl) on each treatment group at 6 months post transplantation. | 6 months | 
| Evolution of Anti-HLA Antibodies (PRA) From Basal to Month 6 Post-transplantation. | HLAs corresponding to MHC (major histocompatibility complex) class I (A, B, and C) present peptides from inside the cell. HLAs corresponding to MHC class II (DP, DM, DO, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. | 6 months | 
| Frequency of Adverse Events or Serious Adverse Events That Occurs During the Study on Each Treatment Group. |  | 6 months | 
| Change on Concentration of Bone Markers (Alkaline Phosphatase) at 6 Months After Transplantation on Each Treatment Group. |  | 6 months | 
| Change on Concentration of Bone Markers (FGF-23) at 6 Months After Transplantation on Each Treatment Group |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplantation, Hyperparathyroidism, Hyperparathyroidism Secondary, Paricalcitol, Calcifediol, Parathyroid hormone