Clinical trial NCT00800358: Safety and Efficacy Study of Paricalcitol Versus Calcitriol in the Treatment of Secondary Hyperparathyroidism
Official title: A Multi Centre, Open Label, Parallel Group, Randomized Controlled Trial to Compare the Safety and Efficacy of Oral Paricalcitol Versus Oral Calcitriol in the Treatment of Secondary Hyperparathyroidism in Dialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hyperparathyroidism
Kidney Disease
Keywords: Secondary hyperparathyroidism
End stage renal disease
Haemodialysis
Peritoneal dialysis
Paricalcitol (Zemplar)
Calcitriol
Lead sponsor: Penang Hospital, Malaysia
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, Malaysia
First posted: 2008-12-02
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether oral paricalcitol is safer and more efficacious compared to oral calcitriol in the treatment of hyperparathyroidism in chronic kidney disease patients undergoing dialysis.

Detailed description: Secondary hyperparathyroidism, a common consequence of chronic kidney disease, results from abnormal regulation of calcium and phosphate homeostasis. The early administration of calcium supplements or vitamin D attenuates the development and progression of hyperparathyroidism, preventing or retarding the emergence of many of the serious complications of chronic kidney disease. However, these vitamin D derivatives also have serious side effects, including hypercalcemia and hyperphosphatemia and, as a result, a high level of the calcium-phosphate product. These adverse outcomes have prompted the development of novel, "nonhypercalcemic" vitamin D analogues. Three of these analogues have recently been marketed for clinical use in patients with chronic kidney disease: 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol), 1 -hydroxyvitamin D2 (doxercalciferol), and 22-oxacalcitriol.

Oral paricalcitol was developed to provide a convenient, alternative therapy, particularly for Peritoneal Dialysis patients in whom regular intravenous administration of paricalcitol is not practical. This study is designed to determine the proportion of patients with 'End stage renal failure' on haemodialysis or peritoneal dialysis and secondary hyperparathyroidism who achieved more than 30% reduction in baseline iPTH concentration at 24 weeks of treatment with Paricalcitol or Calcitriol capsules.

Eligibility criteria: Inclusion Criteria:

* Age at or above 18 years
* End stage renal disease on regular maintenance haemodialysis or peritoneal dialysis for at least 3 months
* iPTH level of 300 pg/ml or greater at baseline
* Written informed consent by subject or guardian
* Female patients will either be post-menopausal for more than 2 years, surgically sterile or if of childbearing age, using double contraception

Exclusion Criteria:

* Baseline calcium value more than 2.87 mmol/L
* Baseline Ca x P of greater than 5.63 mmol2/l2
* Positive for HBsAg or Hepatitis C with raised ALT twice above upper limit of normal or evidence of liver cirrhosis
* Clinically significant gastrointestinal disease
* History of allergic reaction to calcitriol or other vitamin D compounds
* Inability or unwillingness to provide written consent.
* Inability or unwillingness to comply with the requirements of the protocol as determined by the investigator.
* Pregnancy, breastfeeding or use of non-reliable method of contraception.
* Use of medications prohibited prior to randomization such as ketoconazole and other strong P450 3A inhibitors including atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir
* Necessity for calcitonin, biphosphonates, maintenance oral or intravenous glucocorticoid or cinacalcet or other drugs that may affect calcium or bone metabolism.
* Alcohol or substance abuse within 6 months prior to screening
* Other medical condition which, in the investigator's judgement, may be associated with increased risk to the subject or may interfere with study assessments or outcomes.
* Participation in another clinical trial and/or receipt of investigational drugs within 4 weeks prior to screening visit.
* If PD subjects had active peritonitis within one month prior to the screening visit

Primary outcomes:
measure: More than 30% reduction in baseline iPTH concentration at 24 weeks of treatment with Paricalcitol or Calcitriol capsules.
timeFrame: 24 weeks
Secondary outcomes:
measure: Quantum of reduction in alkaline phosphatase level, Time duration to achieve the target level of iPTH. (Titration time), Serum Calcium, phosphate, Ca x Po4 product change from baseline
timeFrame: 24 weeks
measure: Incidence of hypercalcaemic episodes
timeFrame: Through out 24 weeks of participation from the time of enrollment
Other outcomes:
Locations:
city: Alor Star
country: Malaysia
facility: Hospital Sultanah Bahiyah Haemodialysis Unit KM 6 Jalan Langgar
state: Kedah
city: Kota Bahru
country: Malaysia
facility: Hemodialysis Unit, Raja Perempuan Zainab II Hospital
state: Kelantan
city: Kuantan
country: Malaysia
facility: Hemodialysis Unit, Tengku Ampuan Afzan Hospital
state: Pahang
city: Georgetown
country: Malaysia
facility: Clinical Research Centre, Penang Hospital
state: Penang
city: Seberang jaya
country: Malaysia
facility: Haemodialysis Unit, Seberang Jaya Hospital
state: Penang
city: Taiping
country: Malaysia
facility: Hemodialysis Unit, Taiping Hospital
state: Perak
city: Klang
country: Malaysia
facility: Nephrology Department, Tengku Ampuan Rahimah Hospital
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Hemodialysis Unit, Kuala Lumpur Hospital
state: Selangor
city: Serdang
country: Malaysia
facility: Haemodialysis Unit, Serdang Hospital
state: Selangor
city: Seremban
country: Malaysia
facility: Hemodialysis Unit, Tuanku Ja'afar Seremban Hospital
state: Selangor
city: Melaka
country: Malaysia
facility: Haemodialysis Unit, Melaka Hospital
Study officials:
affiliation: Clinical Research Centre, Penang Hospital
name: Ong L Meng, MBBS, MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ong LM, Narayanan P, Goh HK, Manocha AB, Ghazali A, Omar M, Mohamad S, Goh BL, Shah S, Seman MR, Vaithilingam I, Ghazalli R, Rahmat K, Shaariah W, Ching CH; Oral Paricalcitol in ESRD Study Group. Randomized controlled trial to compare the efficacy and safety of oral paricalcitol with oral calcitriol in dialysis patients with secondary hyperparathyroidism. Nephrology (Carlton). 2013 Mar;18(3):194-200. doi: 10.1111/nep.12029.