Oral Paricalcitol in Stage 3 - 5 Chronic Kidney Disease

NCT ID: NCT00796679

Last Updated: 2017-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-06-30

Brief Summary

The purpose of this study is to test the hypothesis that selective vitamin D receptor activation reduces left ventricular hypertrophy and ameliorates inflammation and atherosclerosis in stage 3 -5 chronic kidney disease.

Detailed Description

Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease. According to a previous study, only 15.6% of the patients beginning dialysis therapy had a normal echocardiogram, with left ventricular hypertrophy, left ventricular dilatation and systolic dysfunction occurring in 40.7%, 28% and 15.6% of patients, respectively. In addition, these patients are at an accelerated risk of developing atherosclerosis. The Kidney Disease Outcome Quality Initiative guideline recently raised concerns of a high prevalence of vitamin D deficiency in chronic kidney disease patients not yet requiring dialysis treatment. In addition, very recent data suggested that vitamin D deficiency is an important predictor of mortality in end-stage renal disease patients. Furthermore, hemodialysis patients treated with paricalcitol, a selective vitamin D receptor activator, showed a significantly lower risk of cardiovascular death than those not receiving vitamin D therapy. A number of studies also showed positive benefit of vitamin D receptor activator treatment on regression of left ventricular hypertrophy in dialysis patients. However, there is so far no data in patients with stage 3 and 4 chronic kidney disease where a high prevalence of vitamin D deficiency and cardiac hypertrophy has been reported.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

paricalcitol

Group Type: EXPERIMENTAL

paricalcitol

Intervention Type: DRUG

oral paricalcitol capsule 1 microgram once daily if iPTH \<500pg/mL or 2 microgram once daily if iPTH \>=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year.

2

placebo

Group Type: PLACEBO_COMPARATOR

paricalcitol

Intervention Type: DRUG

oral paricalcitol capsule 1 microgram once daily if iPTH \<500pg/mL or 2 microgram once daily if iPTH \>=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year.

Interventions

paricalcitol

oral paricalcitol capsule 1 microgram once daily if iPTH \<500pg/mL or 2 microgram once daily if iPTH \>=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year.

Intervention Type: DRUG

Other Intervention Names

Zemplar

Eligibility Criteria

Inclusion Criteria

• Patient with stage 3 -5 chronic kidney disease (that is, eGFR < 60 ml/min per 1.73m2) diagnosed for more than 2 months and not expected to start dialysis within the next 12 months, and
• Patient with screening echocardiography showing evidence of left ventricular hypertrophy
• Patient has not received vitamin D therapy in the previous 4 weeks
• For entry into the Treatment Phase, the subject must have:

• screening iPTH >= 55 pg/ml or 5.8pmol/L (determined by the Nichols second-generation assay or similar assay)
• serum calcium < 10.2 mg/dL (2.55 mmol/L)
• serum phosphorus =< 5.2mg/dL (1.68mmol/L)
• Ca*P product < 54 mg2/dL2 (4.36mmol2/L2)
• If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or is of childbearing potential and practicing birth control measures.
• Patients who provide informed consent for the study

Exclusion Criteria

• Patient with a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds.
• Patient with history of renal stones
• Patient with current malignancy
• Patients with clinically significant gastrointestinal disease or liver disease
• Patient with acute renal failure in the recent three months
• Patient with a history of drug or alcohol abuse within six months prior to the screening phase
• Patient is known to be human immunodeficiency virus (HIV) positive.
• Patient with evidence of poor compliance with diet and medication.
• Patient currently receiving medications that may affect calcium, phosphorus metabolism such as calcitonin, cinacalcet, bisphophonates or vitamin D compounds (other than study drug), or other drugs that may affect calcium or bone metabolism, other than females on stable estrogen and/or progestin therapy.
• Patients with active granulomatous disease
• Patient with pregnancy
• Patients currently receiving glucocorticoid steroid or other immunosuppressive treatment or had been administered glucocorticoid or other immunosuppressive treatment for more than 14 days within recent 6 months.
• Patients with contraindication for MRI examination

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Dr. Angela Yee-Moon Wang

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Angela YM Wang, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

Queen Mary Hospital, University of Hong Kong

Locations

Queen Mary Hospital

Hong Kong, , Hong Kong

University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

Countries

Hong Kong

References

Wang AY, Fang F, Chan J, Wen YY, Qing S, Chan IH, Lo G, Lai KN, Lo WK, Lam CW, Yu CM. Effect of paricalcitol on left ventricular mass and function in CKD--the OPERA trial. J Am Soc Nephrol. 2014 Jan;25(1):175-86. doi: 10.1681/ASN.2013010103. Epub 2013 Sep 19.

Reference Type: DERIVED

PMID: 24052631 (View on PubMed)

Other Identifiers

A10-003

Identifier Type: -

Identifier Source: org_study_id