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

• Sponsor: Fundación Senefro (Other)
• Overall Status: Completed
• CT.gov ID: NCT01939977
• Collaborator: AbbVie (Industry), Effice Servicios Para la Investigacion S.L. (Industry)
• Enrollment: 148
• Locations: 16
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Secondary Hyperparathyroidism Due to Renal Causes	Drug: Paricalcitol; Drug: Calcifediol	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Paricalcitol in the Reduction of Secondary Hyperparathyroidism After Renal Transplantation.
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paricalcitol Paricalcitol oral capsules.	Drug: Paricalcitol; 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.; Other Names: Zemplar
Active Comparator: Calcifediol Calcifediol oral drops.	Drug: Calcifediol; 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.; Other Names: Hidroferol

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With iPTH Serum Concentration >110 pg/mL. [6 months]

   Percentage of patients with iPTH serum concentration >110 pg/mL 6 month after transplant.

Secondary Outcome Measures

1. Change on iPTH Serum Concentration. Intention to Treat Analysis. [6 months]

   Change on iPTH serum concentration on each treatment group 6 month post transplantation.

2. Percentage of Patients That Reach at Least a 30% iPTH Reduction at the End of the Study. [6 months]

3. Percentage of Patients With iPTH Levels Between 70-110 pg/mL at the End of the Study. ITT. [6 month]

4. Percentage of Patient With Presence of Calcifications on Protocol Renal Biopsies at 6 Months After Treatment in Each Treatment Group. [6 months]

5. Patients That Suffered the Following Events: Acute Rejection, Acute Rejection Confirmed With Biopsy and/or Subclinic Rejection and/or Chronic Damage. [6 months]

   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. Change on Concentration of Bone Markers (Osteocalcin) at 6 Months After Transplantation on Each Treatment Group. [6 months]

7. Percentage of Patients With Acute Rejection at 6 Months After Transplantation and Treatment on Each Treatment Group. [6 months]

8. Percentage of Patients With Microalbuminuria on Months 1, 3 and 6 Post Transplantation. [Months 1, 3 and 6]

9. Percentage of Patients on Each Stage of Renal Function on Months 1, 3 and 6 Post Transplantation. [Months 1, 3 and 6]

10. Evolution of Speed of Pulse Wave From Month 1 to Month 6 Post Transplantation. [6 months.]

    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.

11. Percentage of Patients With Hypercalcemia on Each Treatment Group at 6 Months Post Transplantation. [6 months]

    Percentage of patients with hypercalcemia (defined as serum calcium levels > 10,3 mg/dl) on each treatment group at 6 months post transplantation.

12. Evolution of Anti-HLA Antibodies (PRA) From Basal to Month 6 Post-transplantation. [6 months]

    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.

13. Frequency of Adverse Events or Serious Adverse Events That Occurs During the Study on Each Treatment Group. [6 months]

14. Change on Concentration of Bone Markers (Alkaline Phosphatase) at 6 Months After Transplantation on Each Treatment Group. [6 months]

15. Change on Concentration of Bone Markers (FGF-23) at 6 Months After Transplantation on Each Treatment Group [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitari Germans Trias I Pujol de Badalona	Badalona	Barcelona	Spain	08916
2	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona	Spain	08907
3	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
4	Hospital Del Mar	Barcelona		Spain	08003
5	Fundació Puigvert-Iuna	Barcelona		Spain	08025
6	Hospital Universitari Vall D'Hebron	Barcelona		Spain	08035
7	Hospital Puerta Del Mar	Cádiz		Spain	11009
8	Hospital Reina Sofía	Córdoba		Spain	14004
9	Complexo Hospitalario Universitario A Coruna	La Coruna		Spain	15006
10	Complejo Hospitalario Universitario de Canarias	Las Palmas De Gran Canaria		Spain	38320
11	Hospital Ramón Y Cajal	Madrid		Spain	28034
12	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
13	Complejo Hospitalario Regional de Málaga	Málaga		Spain	29010
14	Hospital Virgen Del Rocío	Sevilla		Spain	41013
15	Hospital Universitari I Politècnic La Fe	Valencia		Spain	46026
16	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

• Fundación Senefro
• AbbVie
• Effice Servicios Para la Investigacion S.L.

Investigators

• Principal Investigator: Josep M Cruzado, Dr, Fundación SENEFRO - Hospital Universitario de Bellvitge - Barcelona.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fundación Senefro
• ClinicalTrials.gov Identifier: NCT01939977
• Other Study ID Numbers: ACA-SPAI-11-24; 2013-001326-25
• First Posted: Sep 11, 2013
• Last Update Posted: Nov 19, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Fundación Senefro: Hyperparathyroidism; Hyperparathyroidism Secondary; Paricalcitol; Calcifediol; Parathyroid hormone; Renal transplantation
• Additional relevant MeSH terms: Neoplasm Metastasis; Hyperparathyroidism; Hyperparathyroidism, Secondary; Calcifediol

Study Results

Participant Flow

Recruitment Details	94 patients were randomized, but a total of 148 patients were recruited from January 2014 to February 2015.
Pre-assignment Detail	54 of 148 patients were excluded: 48 due to Screening failure and 6 for other reasons.

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Period Title: Overall Study
STARTED	46	48
COMPLETED	37	41
NOT COMPLETED	9	7

Baseline Characteristics

Arm/Group Title	Paricalcitol	Calcifediol	Total
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.	Total of all reporting groups
Overall Participants	46	47	93
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.93 (13.05)	56.15 (14.48)	57.53 (13.79)
Sex: Female, Male (Count of Participants)
Female	14 30.4%	16 34%	30 32.3%
Male	32 69.6%	31 66%	63 67.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
iPTH>110 pg/ml	9 19.6%	16 34%
iPTH<=110 pg/ml	32 69.6%	27 57.4%
N missing	5 10.9%	4 8.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paricalcitol, Calcifediol
	Comments	Taking "per protocol" population, the percentage of patients with iPTH> 110 pg / ml at 6 months post-transplant treated with Paricalcitol was statistically lower than in patients treated with Calcifediol
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0083
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Change on iPTH Serum Concentration. Intention to Treat Analysis.
Description	Change on iPTH serum concentration on each treatment group 6 month post transplantation.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	41	43
iPTH at month 6	75.63 (55.5)	101.27 (55.1)
iPTH at baseline	338.48 (135.3)	315.47 (117.7)

3. Secondary Outcome

Title	Percentage of Patients That Reach at Least a 30% iPTH Reduction at the End of the Study.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Reduction iPTH>=30%	39 84.8%	38 80.9%
Reduction iPTH<30%	2 4.3%	5 10.6%
N missing	5 10.9%	4 8.5%

4. Secondary Outcome

Title	Percentage of Patients With iPTH Levels Between 70-110 pg/mL at the End of the Study. ITT.
Time Frame	6 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	41	43
iPTH<70 pg/ml	26 56.5%	16 34%
iPTH 70-110 pg/ml	6 13%	11 23.4%
iPTH >110 pg/ml	9 19.6%	16 34%

5. Secondary Outcome

Title	Percentage of Patient With Presence of Calcifications on Protocol Renal Biopsies at 6 Months After Treatment in Each Treatment Group.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	17	19
Calcifications	1 2.2%	0 0%
No calcifications	16 34.8%	19 40.4%

6. Secondary Outcome

Title	Patients That Suffered the Following Events: Acute Rejection, Acute Rejection Confirmed With Biopsy and/or Subclinic Rejection and/or Chronic Damage.
Description	Patients with at least one of the following events: acute rejection, acute rejection confirmed with biopsy and/or subclinic rejection and/or chronic damage.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Patients with at least one event	14 30.4%	6 12.8%
Patients with no events	12 26.1%	15 31.9%
N missing	20 43.5%	26 55.3%

7. Secondary Outcome

Title	Change on Concentration of Bone Markers (Osteocalcin) at 6 Months After Transplantation on Each Treatment Group.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This value was missing for some patients at month 6

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Baseline Osteocalcin	11.74 (9.2)	12.62 (8.5)
Month 6 Osteocalcin	4.02 (3.6)	5.20 (4.1)

8. Secondary Outcome

Title	Percentage of Patients With Acute Rejection at 6 Months After Transplantation and Treatment on Each Treatment Group.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Yes	5 10.9%	2 4.3%
No	41 89.1%	45 95.7%

9. Secondary Outcome

Title	Percentage of Patients With Microalbuminuria on Months 1, 3 and 6 Post Transplantation.
Time Frame	Months 1, 3 and 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Normal (UACR<30 mg/g)	18 39.1%	16 34%
UACR 30-300 mg/g	3 6.5%	1 2.1%
N missing	25 54.3%	30 63.8%
Normal (UACR<30 mg/g)	13 28.3%	12 25.5%
UACR 30-300 mg/g	3 6.5%	0 0%
N missing	30 65.2%	35 74.5%
Normal (UACR<30 mg/g)	16 34.8%	14 29.8%
UACR 30-300 mg/g	1 2.2%	0 0%
N missing	29 63%	33 70.2%

10. Secondary Outcome

Title	Percentage of Patients on Each Stage of Renal Function on Months 1, 3 and 6 Post Transplantation.
Time Frame	Months 1, 3 and 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
eGFR >=90	1 2.2%	4 8.5%
eGFR 60-89	5 10.9%	5 10.6%
eGFR 30-59	29 63%	27 57.4%
eGFR 15-29	6 13%	9 19.1%
eGFR<15	3 6.5%	1 2.1%
N missing	2 4.3%	1 2.1%
eGFR >=90	2 4.3%	2 4.3%
eGFR 60-89	2 4.3%	10 21.3%
eGFR 30-59	26 56.5%	25 53.2%
eGFR 15-29	8 17.4%	8 17%
eGFR<15	2 4.3%	0 0%
N missing	6 13%	2 4.3%
eGFR >=90	1 2.2%	3 6.4%
eGFR 60-89	5 10.9%	9 19.1%
eGFR 30-59	24 52.2%	25 53.2%
eGFR 15-29	9 19.6%	5 10.6%
eGFR<15	2 4.3%	1 2.1%
N missing	5 10.9%	4 8.5%

11. Secondary Outcome

Title	Evolution of Speed of Pulse Wave From Month 1 to Month 6 Post Transplantation.
Description	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.
Time Frame	6 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	17	14
Speed pulse wave gets better at month 6	1 2.2%	1 2.1%
Speed pulse wave maintained	14 30.4%	12 25.5%
Speed pulse wave gets worse at month 6	2 4.3%	1 2.1%

12. Secondary Outcome

Title	Percentage of Patients With Hypercalcemia on Each Treatment Group at 6 Months Post Transplantation.
Description	Percentage of patients with hypercalcemia (defined as serum calcium levels > 10,3 mg/dl) on each treatment group at 6 months post transplantation.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Serum Ca >10,3 mg/dl	3 6.5%	2 4.3%
Serum Ca <=10,3 mg/dl	39 84.8%	41 87.2%
N missing	4 8.7%	4 8.5%

13. Secondary Outcome

Title	Evolution of Anti-HLA Antibodies (PRA) From Basal to Month 6 Post-transplantation.
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	40	42
Positive class I	1 2.2%	0 0%
Positive class II	3 6.5%	4 8.5%
Positive class I and II	1 2.2%	1 2.1%
Negative	35 76.1%	37 78.7%
Positive class I	1 2.2%	0 0%
Positive class II	6 13%	3 6.4%
Positive class I and II	1 2.2%	1 2.1%
Negative	32 69.6%	38 80.9%

14. Secondary Outcome

Title	Frequency of Adverse Events or Serious Adverse Events That Occurs During the Study on Each Treatment Group.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Patients with adverse event (AE)	41 89.1%	38 80.9%
Patients with possibly or probably related AE	2 4.3%	1 2.1%
Patients with serious adverse event (SAE)	24 52.2%	20 42.6%
Patients with possibly or probably related SAE	0 0%	0 0%
Patients with AE that leads to discontinuation	2 4.3%	4 8.5%
Patients with moderate-severe adverse event	34 73.9%	28 59.6%

15. Secondary Outcome

Title	Change on Concentration of Bone Markers (Alkaline Phosphatase) at 6 Months After Transplantation on Each Treatment Group.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This value was missing for some patients at month 6

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Baseline alkaline phosphatase	13.85 (6.9)	14.50 (7.4)
Month 6 alkaline phosphatase	11.68 (9.1)	11.79 (5.1)

16. Secondary Outcome

Title	Change on Concentration of Bone Markers (FGF-23) at 6 Months After Transplantation on Each Treatment Group
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This value was missing for some patients

Arm/Group Title	Paricalcitol	Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.	Calcifediol oral drops. Calcifediol: 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.
Measure Participants	46	47
Baseline FGF-23	2039.13 (3559.8)	1359.56 (7112.9)
Month 6 FGF-23	1937.30 (3738.0)	289.14 (945.1)

Adverse Events

Time Frame	Adverse events collected during the participation in the study (6 months). Non serious adverse events: only reported here the study medication related adverse events.
Arm/Group Title	Paricalcitol		Calcifediol
Arm/Group Description	Paricalcitol oral capsules. Paricalcitol: 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.		Calcifediol oral drops. Calcifediol: 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.
All Cause Mortality
	Paricalcitol		Calcifediol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/47 (0%)
Serious Adverse Events
	Paricalcitol		Calcifediol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/46 (52.2%)		20/47 (42.6%)
Blood and lymphatic system disorders
Thrombotic microangiopathy	1/46 (2.2%)	1	0/47 (0%)	0
Neutropenia	0/46 (0%)	0	1/47 (2.1%)	1
Cardiac disorders
Heart failure	1/46 (2.2%)	1	0/47 (0%)	0
Gastrointestinal disorders
Diarrhea	0/46 (0%)	0	1/47 (2.1%)	1
Anal bleeding	0/46 (0%)	0	1/47 (2.1%)	1
General disorders
Extravasation	0/46 (0%)	0	1/47 (2.1%)	1
Pirexia	2/46 (4.3%)	2	0/47 (0%)	0
Hepatobiliary disorders
Cholangitis	1/46 (2.2%)	1	0/47 (0%)	0
Acute cholecystitis	1/46 (2.2%)	1	0/47 (0%)	0
Immune system disorders
Allograft rejection	1/46 (2.2%)	1	1/47 (2.1%)	1
Infections and infestations
Infections	11/46 (23.9%)	11	6/47 (12.8%)	7
Positive test for Pseudomonas	0/46 (0%)	0	1/47 (2.1%)	1
Injury, poisoning and procedural complications
Surgical wound	1/46 (2.2%)	1	1/47 (2.1%)	1
Metabolism and nutrition disorders
Hyperpotasemia	1/46 (2.2%)	1	0/47 (0%)	0
Dehydratation	0/46 (0%)	0	1/47 (2.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cells carcinoma	0/46 (0%)	0	1/47 (2.1%)	1
Nervous system disorders
Depressed level of consciousness	1/46 (2.2%)	1	0/47 (0%)	0
Metabolic encephalopathy	0/46 (0%)	0	1/47 (2.1%)	1
Renal and urinary disorders
Impaired renal function	1/46 (2.2%)	1	0/47 (0%)	0
Impaired renal function	7/46 (15.2%)	8	3/47 (6.4%)	3
Ureteral dilation	1/46 (2.2%)	1	0/47 (0%)	0
Hematuria	0/46 (0%)	0	2/47 (4.3%)	2
Acute kidney injury	0/46 (0%)	0	1/47 (2.1%)	1
Proteinuria	0/46 (0%)	0	1/47 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/46 (0%)	0	1/47 (2.1%)	1
Dyspnea	1/46 (2.2%)	1	1/47 (2.1%)	1
Acute pulmonary edema	1/46 (2.2%)	1	0/47 (0%)	0
Pulmonary embolia	0/46 (0%)	0	1/47 (2.1%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	1/46 (2.2%)	1	0/47 (0%)	0
Surgical and medical procedures
Transplantectomy	0/46 (0%)		1/47 (2.1%)
Lymphocele marsupialization	1/46 (2.2%)		0/47 (0%)
Vascular disorders
Hematoma	0/46 (0%)	0	1/47 (2.1%)	1
Lymphocele	1/46 (2.2%)	2	0/47 (0%)	0
Other (Not Including Serious) Adverse Events
	Paricalcitol		Calcifediol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/46 (4.3%)		1/47 (2.1%)
Endocrine disorders
Parotiditis	0/46 (0%)	0	1/47 (2.1%)	1
Metabolism and nutrition disorders
Hypercalcemia	2/46 (4.3%)	2	0/47 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.