Treatment of Secondary Hyperparathyroidism in the Uremic Patient

Treatment of Secondary Hyperparathyroidism in the Uremic Patient. A Study Comparing Alfacalcidol and Paricalcitol

The purpose of this study is to compare alfacalcidol and paricalcitol in the treatment of secondary hyperparathyroidism in hemodialysis patients.

Study Overview

• Status: Terminated
• Conditions: Vitamin D Deficiency; Chronic Kidney Disease; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: paricalcitol; Drug: alfacalcidol

Detailed Description

Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its clinical consequences include renal osteodystrophy, calciphylaxia and potentially vascular calcifications with increased morbidity and mortality.

Reduced synthesis of active vitamin D contributes to secondary hyperparathyroidism. Therefore we primarily manage this condition with activated vitamin D. In Denmark alfacalcidol is the primary choice of vitamin D analog.

However hypercalcemia and hyperphosphatemia may limit the use of alfacalcidol therapy due to increased risk of vascular calcification and mortality.

Therefore a new vitamin D analog, paricalcitol, has been developed, that may be less prone to develop hypercalcemia and hyperphosphatemia.

However a randomised controlled clinical study comparing alfacalcidol and paricalcitol has never been performed.

The primary objective of this study is to evaluate the effect of alfacalcidol and paricalcitol on intact parathyroid hormone level and the tendency towards hyperphosphatemia and hypercalcemia.

The study is performed in 117 patients with end stage renal failure on maintenance hemodialysis therapy in 6 different Danish hemodialysis units.

The design is a multicenter crossover study where patients are randomized into two treatment arms. After a wash out period of 6 weeks they are receiving alfacalcidol or paricalcitol for a period of 16 weeks and after a further wash out period of 6 weeks they receive the contrary treatment (respectively paricalcitol or alfacalcidol) for 16 weeks.

The initial dose of alfacalcidol (1 μg intravenously after dialysis) and paricalcitol (3 μg intravenously after dialysis) will be adjusted every second week based on iPTH, p-calcium and p-phosphate.

P-calcium, p-phosphate, iPTH, pulse and blood pressure are measured every second week. By the beginning and the end of each period of treatment, alkaline phosphatase, 25OH-D3, 1,25 (OH)2 vitamin D and safety parameters are measured, pulse wave velocity and pulse wave analysis is performed in a subgroup.

Alfacalcidol and paricalcitol are both registered treatment modalities for patients with renal failure and secondary hyperparathyroidism and should not perform any risk for the safety of the enrolled patients as well as the blood sampling and blood pressure measurement should not perform any risk either.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 4000
    • Aalborg University Hospital
  • Aarhus, Denmark, 4000
    • Arhus University Hospital Skejby
  • Esbjerg, Denmark, 6700
    • Hospital of Southwest Denmark Esbjerg
  • Holbæk, Denmark, 4300
    • Holbæk County Hospital
  • Holstebro, Denmark, 7500
    • Holstebro County Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital
  • Roskilde, Denmark, 4000
    • Roskilde County Hospital
  • Viborg, Denmark, 8800
    • Viborg County Hospital

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:

1. >18 years old
2. Secondary hyperparathyroidism; iPTH > 350 pg/ml before any treatment or after 6 weeks without any treatment with vitamin D.
3. Chronic renal insufficiency receiving hemodialysis.
4. P-phosphate < 1,8 mmol/l
5. P-calcium ion < 1,25 mmol/l
6. Receiving maximal possible dose of calcium-based phosphate binder.
7. Accepting 2 x 6 weeks without vitamin D.
8. Safe anti conception in fertile women
9. Do not expect need of calcimimetics or parathyroidectomy during the next year.
10. Written informed consent.

Exclusion Criteria:

1. Malignancy
2. Disease or condition making the patient unable to participate
3. Expected lifetime less than one year.
4. Pregnancy and nursing
5. Allergic to contents of Zemplar or Etalpha
6. Currently receiving calcimimetics
7. Participating in other clinical intervention studies

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; alfacalcidol 16 weeks, 6 weeks wash out, paricalcitol 16 weeks	Drug: paricalcitol; 3 microg 3 times a week. dosage is increased/decreased 50 % every second week according to iPTH, ionised s-calcium and phosphate; Other Names: Zemplar
Active Comparator: 2; paricalcitol ´16 weeks, 6 weeks wash out, alfacalcidol 16 weeks	Drug: alfacalcidol; 1 microg 3 times a week, dosage is titrated every second week according to iPTH, phosphate and ionised s-calcium.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The effect of alfacalcidol and paricalcitol on intact parathyroid hormone level and the tendency towards hyperphosphatemia and hypercalcemia	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
alkaline phosphatase, 25OH-vitamin D,1,25 OH2-vitamin D,calcium x phosphate product, blood pressure, pulse, pulse pressure, parathyroidectomy, pulse wave velocity and pulse wave analysis, initiation of treatment with calcimimetics.	16 weeks

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Investigators: Principal Investigator: Ditte Hansen, MD, Zealand University Hospital

Publications and helpful links

General Publications

• Hansen D, Rasmussen K, Rasmussen LM, Bruunsgaard H, Brandi L. The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study. BMC Nephrol. 2014 Aug 12;15:130. doi: 10.1186/1471-2369-15-130.
• Hansen D, Brandi L, Rasmussen K. Treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol. BMC Nephrol. 2009 Sep 24;10:28. doi: 10.1186/1471-2369-10-28.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Anticipated): September 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimate): May 4, 2007

Study Record Updates

• Last Update Posted (Estimate): April 4, 2011
• Last Update Submitted That Met QC Criteria: April 1, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Kidney Failure, Chronic; Renal Insufficiency, Chronic; Hemodialysis; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Renal Osteodystrophy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Nutrition Disorders; Parathyroid Diseases; Neoplastic Processes; Avitaminosis; Deficiency Diseases; Malnutrition; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Alfacalcidol; Hydroxycholecalciferols
• Other Study ID Numbers: EudraCT 2006-005981-37