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

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

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 Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism Due to Renal Causes
• Intervention / Treatment: Drug: Paricalcitol; Drug: Calcifediol

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 Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08025
    • Fundació Puigvert-Iuna
  • Cádiz, Spain, 11009
    • Hospital Puerta del Mar
  • Córdoba, Spain, 14004
    • Hospital Reina Sofia
  • La Coruna, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña
  • Las Palmas De Gran Canaria, Spain, 38320
    • Complejo Hospitalario Universitario de Canarias
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Málaga, Spain, 29010
    • Complejo Hospitalario Regional de Málaga
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias I Pujol de Badalona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundación Senefro
• Collaborators: AbbVie; Effice Servicios Para la Investigacion S.L.
• Investigators: Principal Investigator: Josep M Cruzado, Dr, Fundación SENEFRO - Hospital Universitario de Bellvitge - Barcelona.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: August 28, 2013
• First Submitted That Met QC Criteria: September 6, 2013
• First Posted (ESTIMATE): September 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 19, 2018
• Last Update Submitted That Met QC Criteria: May 18, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Hyperparathyroidism; Renal transplantation; Parathyroid hormone; Paricalcitol; Calcifediol; Hyperparathyroidism Secondary
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcifediol
• Other Study ID Numbers: ACA-SPAI-11-24; 2013-001326-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO