Comparative Effects of Doxercalciferol and Calcitriol on Secondary Hyperparathyroidism in ESRD

Effects of Doxercalciferol Compared to Calcitriol for Lowering PTH Level in Hemoodialysis Patients

Secondary hyperparathyroidism (SHPT) is a common complication of advanced chronic kidney disease (CKD), caused by phosphate retention and vitamin D deficiency, leading to elevated parathyroid hormone (PTH) levels and increased bone and cardiovascular complications. Active vitamin D analogs such as calcitriol and doxercalciferol are used to suppress PTH levels, though they differ in pharmacologic properties and effects on mineral metabolism. Intravenous preparations may offer improved bioavailability and adherence in hemodialysis patients.This randomized controlled trial will be conducted in the Department of Nephrology at Chittagong Medical College Hospital among 98 adult hemodialysis patients with SHPT. Participants will be randomly assigned to receive either intravenous doxercalciferol or oral calcitriol. The study aims to compare their effectiveness in lowering PTH levels and evaluate safety outcomes.

Continuous variables will be expressed as mean ± standard deviation, while categorical variables will be presented as frequencies and percentages. Independent t-tests, chi-square tests, or Fisher's exact tests will be used for statistical comparisons. Data analysis will be performed using SPSS version 27.0, with a p-value <0.05 considered statistically significant.

Study Overview

• Status: Not yet recruiting
• Conditions: Lowering Parathyroid Hormone Level in Patients on Hemodioalysis
• Intervention / Treatment: Drug: Doxercalciferol administration; Drug: oral calcitriol 0.25 microgram

Detailed Description

Secondary hyperparathyroidism (SHPT), characterized by markedly elevated parathyroid hormone (PTH) levels, arises from the metabolic abnormalities associated with end-stage renal disease (ESRD). It affects the majority of patients undergoing dialysis and contributes to a wide range of complications, including cognitive impairment, bone disease, and cardiovascular morbidity. SHPT develops early during chronic kidney disease (CKD), often beginning in stage G2, when impaired phosphate excretion stimulates increased secretion of PTH. As kidney function declines further, hyperphosphatemia and hypocalcemia become more pronounced, leading to progressive parathyroid gland hyperplasia and excessive hormone production.

Clinically, SHPT is a major component of chronic kidney disease-mineral and bone disorder (CKD-MBD), which is characterized by bone pain, skeletal deformities, spontaneous fractures, soft tissue calcification, and muscle weakness. Persistent elevations in PTH also contribute to vascular calcification, left ventricular hypertrophy, and other cardiovascular complications that significantly increase morbidity and mortality among dialysis patients. Consequently, uncontrolled SHPT adversely affects both quality of life and long-term survival.

Parathyroid hormone plays a central role in calcium and phosphate homeostasis. It maintains serum calcium levels by stimulating bone resorption and enhancing calcium mobilization from the skeleton. Although PTH increases phosphate release from bone, it also promotes phosphate excretion through the kidneys by reducing tubular phosphate reabsorption. In patients with CKD, these regulatory mechanisms become impaired, resulting in chronic elevations of PTH and progressive disturbances in mineral metabolism. Sustained hyperparathyroidism can lead to high-turnover bone disease, renal osteodystrophy, vascular calcification, and increased cardiovascular risk.

Intravenous doxercalciferol and oral calcitriol are commonly used vitamin D receptor activators for the management of SHPT in hemodialysis patients. Calcitriol, the active form of vitamin D, directly binds to vitamin D receptors and effectively suppresses PTH secretion. However, its use is frequently associated with increases in serum calcium and phosphate levels, potentially increasing the risk of vascular calcification. Doxercalciferol, a synthetic vitamin D analog, requires hepatic activation and has been shown to provide effective PTH suppression while producing fewer calcemic effects. These pharmacological differences may influence treatment outcomes and safety profiles in dialysis populations.

Recent evidence suggests that both agents are effective in reducing PTH levels, although intravenous doxercalciferol may offer improved biochemical control and a lower incidence of hypercalcemia. As secondary hyperparathyroidism remains highly prevalent among hemodialysis patients, identifying the most effective and safest therapeutic option is of considerable clinical importance.

In Bangladesh and other low- and middle-income countries, the growing burden of CKD and dependence on maintenance hemodialysis present substantial healthcare challenges. Medication cost, availability, and patient adherence play important roles in treatment selection. Oral calcitriol is widely available and relatively inexpensive, whereas intravenous doxercalciferol may be less accessible in resource-constrained settings. Furthermore, adherence to oral therapy may be affected by pill burden and other practical barriers. Therefore, evidence comparing the efficacy and safety of these treatment options is essential for guiding cost-effective and evidence-based clinical practice.

Despite the widespread use of both agents, high-quality comparative studies in hemodialysis patients from resource-limited settings remain limited. Most available evidence originates from high-income countries, and its applicability to South Asian populations is uncertain. A direct comparison of intravenous doxercalciferol and oral calcitriol with respect to PTH control, biochemical outcomes, safety, and treatment practicality is therefore warranted. This study aims to address this knowledge gap and provide evidence to support optimal management of secondary hyperparathyroidism among hemodialysis patients in resource-constrained environments.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: DR.A.K.M. ARSHADUL ABBAS, MBBS; Phone Number: +8801712985290; Email: arshadulabbas@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients aged 18 years or older.
2. Diagnosed with secondary hyperparathyroidism (SHPT) with elevated serum PTH levels (>300 pg/mL).
3. Undergoing maintenance hemodialysis for at least 3 months.
4. Patients on calcitriol therapy within wash out period 40 hrs.

Exclusion Criteria:

1. Patients with known case of primary hyperparathyroidism or parathyroidectomy.
2. Serum calcium>10mg/dL or phosphate>5.5mg/dL at baseline.
3. Active liver disease or significant hepatic dysfunction, Alcoholism.
4. History of hypersensitivity to vitamin D analogs.
5. Pregnant or breastfeeding women.
6. Concurrent use of medications (e.g. bisphosphonates).
7. Patients with active malignancy.(e.g.Multiple myeloma,Bronchogenic carcinoma)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Doxercalciferol for PTH Reduction in Hemodialysis Patients; Experimental subjects will receive an intravenous loading dose of doxercalciferol 4 micrograms after dialysis, in addition to their standard routine medications. Each Dose of doxercalciferol will be given after skin sensitivity test	Drug: Doxercalciferol administration; receive iv doxercalciferol 4 microgram after dialysis for 12 weeks in addition to their standard routine medications.
Active Comparator: oral Calcitriol for PTH Reduction in Hemodialysis Patients; Control group will receive oral calcitriol 0.25 microgram once daily in addition to their standard routine medications for 12 weeks	Drug: oral calcitriol 0.25 microgram; Control group will receive oral calcitriol 0.25 microgram once daily in addition to their standard routine medications for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum Parathyroid Hormone (PTH) levels	Patients undergoing hemodialysis with secondary hyperparathyroidism will receive intravenous doxercalciferol according to a standardized dosing protocol. The dose will be adjusted based on serum parathyroid hormone (PTH), calcium, and phosphate levels measured periodically. The aim is to evaluate the effectiveness of doxercalciferol in reducing PTH levels	12 weeks

Collaborators and Investigators

• Sponsor: Chittagong Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): July 5, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 59.127.1557.013.19.2025.1237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No