Treatment of Secondary Hyperparathyroidism in the Uremic Patient

Sponsor

Zealand University Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT00469599

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

10.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Secondary Hyperparathyroidism Chronic Kidney Disease Vitamin D Deficiency	Drug: paricalcitol Drug: alfacalcidol	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2007

Anticipated Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

The effect of alfacalcidol and paricalcitol on intact parathyroid hormone level and the tendency towards hyperphosphatemia and hypercalcemia [16 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aalborg University Hospital	Aalborg	Denmark	4000
2	Århus University Hospital Skejby	Aarhus	Denmark	4000
3	Hospital of Southwest Denmark Esbjerg	Esbjerg	Denmark	6700
4	Holbæk County Hospital	Holbæk	Denmark	4300
5	Holstebro County Hospital	Holstebro	Denmark	7500
6	Odense University Hospital	Odense	Denmark	5000
7	Roskilde County Hospital	Roskilde	Denmark	4000
8	Viborg County Hospital	Viborg	Denmark	8800