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

Phase 4

Completed

• Conditions: Secondary Hyperparathyroidism; End Stage Renal Disease
• Interventions: Drug: alfacalcidol and calcitriol

• Registration Number: NCT01115543
• Lead Sponsor: Mahidol University

Brief Summary

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

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 Timeline

• Study Start: 2008-08
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Status Verified: 2010-05
• Study First Submitted: 2010-05-01
• Study First Submitted QC: 2010-05-01
• Last Update Submitted: 2010-05-01
• Study First Posted: 2010-05-04
• Last Update Posted: 2010-05-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
calcitriol	alfacalcidol and calcitriol	The subjects were randomized to receive calcitriol in a dose-escalating fashion for up to 24 weeks.
alfacalcidol	alfacalcidol and calcitriol	-

Primary Outcome Measures

Name	Time	Method
Reduction of intact parathyroid hormone levels	48 weeks

Secondary Outcome Measures

Name	Time	Method
hypercalcemia and hyperphosphatemia	48 weeks	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.

Trial Locations

Locations (1)

Siriraj Medical School; 🇹🇭 Bangkok-noi, Bangkok, Thailand