Clinical trial NCT00469599: Treatment of Secondary Hyperparathyroidism in the Uremic Patient
Official title: Treatment of Secondary Hyperparathyroidism in the Uremic Patient. A Study Comparing Alfacalcidol and Paricalcitol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease
Vitamin D Deficiency
Keywords: Hyperparathyroidism, Secondary
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Vitamin D Deficiency
Renal Osteodystrophy
Hemodialysis
Lead sponsor: Zealand University Hospital
Sponsor class: OTHER
First posted: 2007-05-04
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: The effect of alfacalcidol and paricalcitol on intact parathyroid hormone level and the tendency towards hyperphosphatemia and hypercalcemia
timeFrame: 16 weeks
Secondary outcomes:
measure: 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.
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Århus University Hospital Skejby
city: Esbjerg
country: Denmark
facility: Hospital of Southwest Denmark Esbjerg
city: Holbæk
country: Denmark
facility: Holbæk County Hospital
city: Holstebro
country: Denmark
facility: Holstebro County Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde County Hospital
city: Viborg
country: Denmark
facility: Viborg County Hospital
Study officials:
affiliation: Zealand University Hospital
name: Ditte Hansen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.