Efficacy and Safety of Alfacalcidol Compared to Calcitriol for Treatment of Secondary Hyperparathyroidism

A Randomized Trial Comparing Pulse Calcitriol and Alfacalcidol for the Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients

This study was performed to determine whether calcitriol provides a therapeutic advantage to alfacalcidol for treatment of secondary hyperparathyroidism in ESRD patients.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: alfacalcidol and calcitriol

Detailed Description

Secondary hyperparathyroidism has a significant impact on morbidity and mortality in advanced chronic kidney disease (CKD).Both nonselective and selective vitamin D receptor activators (VDRAs) are demonstrated in many studies for their efficacy on suppression of PTH. Most of them are quite expensive and unavailable in many countries. Calcitriol and alfacalcidol are less expensive and worldwidely distributed. There is only one short-term study which directly compares these two drugs. This study demonstrates that calcitriol is superior to alfacalcidol. However, alfacalcidol is a prohormone of calcitriol. It has to be converted by 25-hydroxylase at the liver to generate 1,25-dihydroxyvitamin D3 to act on target cells. Many pharmacokinetics studies demonstrate that alfacalcidol has lower AUC compared to calcitriol if they are administered in the same dose. Therefore, the authors hypothesize that alfacalcidol may be equivalently efficacious as calcitriol if its dose is adjusted according to the pharmacokinetics studies.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Bangkok-noi, Bangkok, Thailand, 10700
      • Siriraj Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic hemodialysis patients who underwent scheduled hemodialysis for at least 3 months with secondary hyperparathyroidism (intact PTH levels > 300 pg/mL)

Exclusion Criteria:

• (1) age < 18 years (2) hypersensitivity to calcitriol or alfacalcidol (3) inadequate dialysis [defined as single-pooled Kt/V (sp-Kt/V) <1.2 and <2.0 for thrice a week and twice a week hemodialysis] (4) corrected serum calcium >10.2 mg/dL or serum phosphate >6 mg/dL after adjusting dialysate calcium and phosphate binders (5) diameter of parathyroid gland >10 mm (6) pregnancy or lactation (7) liver cirrhosis (8) active kidney transplantation (9) previous parathyroidectomy (10) malignancy or chronic infection/inflammation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: calcitriol; The subjects were randomized to receive calcitriol in a dose-escalating fashion for up to 24 weeks.	Drug: alfacalcidol and calcitriol; The initial dose of alfacalcidol was twice that of calcitriol.Both were adjusted to control intact PTH within the ranges of 150-300 pg/ml.
Experimental: alfacalcidol	Drug: alfacalcidol and calcitriol; The initial dose of alfacalcidol was twice that of calcitriol.Both were adjusted to control intact PTH within the ranges of 150-300 pg/ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction of intact parathyroid hormone levels	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hypercalcemia and hyperphosphatemia	proportion of the patients who achieved a target PTH, changes in plasma calcium and phosphorus, the proportion of the patients who had hypercalcemia (plasma corrected calcium > 10.8 mg/dl), hyperphosphatemia (plasma phosphorus > 6.0 mg/dl) and calcium-phosphorus products > 55 mg2/dl2 between groups.	48 weeks

Collaborators and Investigators

• Sponsor: Mahidol University

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: May 1, 2010
• First Submitted That Met QC Criteria: May 1, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): May 4, 2010
• Last Update Submitted That Met QC Criteria: May 1, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Kidney Failure, Chronic; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Calcitriol; Alfacalcidol; Hydroxycholecalciferols
• Other Study ID Numbers: 358/2551