Oral Paricalcitol in Stage 3 - 5 Chronic Kidney Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 paricalcitol |
Drug: 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.
Other Names:
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| Placebo Comparator: 2 placebo |
Drug: 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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in left ventricular mass index determined by MRI [1 year]
Secondary Outcome Measures
- Change in left atrial and ventricular volumes, systolic and diastolic function, carotid intima-media thickness, flow mediated dilation, pulse wave velocity, serum inflammatory and cardiac biomarkers, intact PTH, 24-hour urine protein and renal function [1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Patient with screening echocardiography showing evidence of left ventricular hypertrophy
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Patient has not received vitamin D therapy in the previous 4 weeks
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For entry into the Treatment Phase, the subject must have:
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screening iPTH >= 55 pg/ml or 5.8pmol/L (determined by the Nichols second-generation assay or similar assay)
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serum calcium < 10.2 mg/dL (2.55 mmol/L)
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serum phosphorus =< 5.2mg/dL (1.68mmol/L)
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Ca*P product < 54 mg2/dL2 (4.36mmol2/L2)
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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.
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Patients who provide informed consent for the study
Exclusion Criteria:
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Patient with a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds.
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Patient with history of renal stones
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Patient with current malignancy
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Patients with clinically significant gastrointestinal disease or liver disease
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Patient with acute renal failure in the recent three months
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Patient with a history of drug or alcohol abuse within six months prior to the screening phase
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Patient is known to be human immunodeficiency virus (HIV) positive.
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Patient with evidence of poor compliance with diet and medication.
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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.
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Patients with active granulomatous disease
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Patient with pregnancy
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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.
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Patients with contraindication for MRI examination
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Queen Mary Hospital | Hong Kong | Hong Kong | 0000 | |
| 2 | University of Hong Kong, Queen Mary Hospital | Hong Kong | Hong Kong | 0000 |
Sponsors and Collaborators
- The University of Hong Kong
- Abbott
Investigators
- Principal Investigator: Angela YM Wang, MD, FRCP, Queen Mary Hospital, University of Hong Kong
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- A10-003