Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000108415
Ethics application status
Approved
Date submitted
16/01/2016
Date registered
1/02/2016
Date last updated
1/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Is the efficacy of nutritional vitamin D (cholecalciferol) comparable to active vitamin D (calcitriol) as maintenance therapy in dialysis dependent chronic kidney disease patients?
Scientific title
Is the efficacy of nutritional vitamin D (cholecalciferol) comparable to active vitamin D (calcitriol) as maintenance therapy in dialysis dependent chronic kidney disease patients?
Secondary ID [1] 288334 0
Nil known
Universal Trial Number (UTN)
U1111-1178-5860
Trial acronym
CHOLCAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic kidney disease 297308 0
Chronic kidney disease-mineral and bone disorder 297309 0
Condition category
Condition code
Renal and Urogenital 297508 297508 0 0
Kidney disease
Metabolic and Endocrine 297509 297509 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a cohort study conducted over 12 weeks at a Regional Renal Centre at Launceston General Hospital and its satellite Kings Meadows Dialysis Unit.
Dialysis dependent stage 5 chronic kidney disease (CKD) patients who have been stable on oral calcitriol therapy for 3 months will be switched over to oral cholecalciferol therapy at the beginning of study period. Conversion of calcitriol to cholecalciferol will be based on the ratio of 0.25 mcg calcitriol to 25 mcg cholecalciferol. If participants are already on both pre-existing cholecalciferol and calcitriol, then calcitriol will be ceased followed by increased cholecalciferol dose based on the conversion ratio earlier. Monthly dispensing of cholecalciferol will be performed by Department of Pharmacy at Launceston General Hospital, to ensure compliance.
Baseline participant characteristics including age, gender, ethnicity, body mass index (BMI), smoking status, primary kidney disease(s), time on dialysis, medical comorbidities, dialysate calcium concentration, phosphate binder prescriptions, pre-existing vitamin D therapy and previous biochemical results will be collected. Medical records will be assessed if needed for the information.
The effects of this new therapy will be studied over the course of 12 weeks, to determine the success or failure of that change in therapy (as defined by ability of cholecalciferol to maintain serum albumin-corrected calcium levels within target range of 2.10 mmol/L to 2.60 mmol/L). Blood specimens will be collected at baseline, 4-week, 8-week and 12-week after patients have been switched to cholecalciferol. Serum calcium, phosphate, intact parathyroid hormone, alkaline phosphatase, and vitamin D (25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3) will be measured to determine the effects. Cholecalciferol dosage will be reviewed at 4-week interval with the blood tests to determine the need for adjustment by the investigators (Nephrologist and Nephorology Advanced Trainee)
Intervention code [1] 293629 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 297068 0
Proportion of participants that can be successfully changed over to oral cholecalciferol from oral calcitriol therapy. The success will be determined by ability of cholecalciferol to maintain albumin-corrected serum calcium level between 2.10 and 2.60 mmol/L.
Timepoint [1] 297068 0
12 weeks post change over
Secondary outcome [1] 319954 0
Serum phosphate level
Timepoint [1] 319954 0
4, 8, 12 weeks post change over
Secondary outcome [2] 320331 0
Serum intact parathyroid hormone level
Timepoint [2] 320331 0
4, 8, 12 weeks post change over
Secondary outcome [3] 320332 0
Serum alkaline phosphatase level
Timepoint [3] 320332 0
4, 8, 12 weeks post change over
Secondary outcome [4] 320333 0
Serum 25-hydroxyvitamin D3 level
Timepoint [4] 320333 0
4, 8, 12 weeks post change over
Secondary outcome [5] 320334 0
Serum 1,25-dihydroxyvitamin D3 level
Timepoint [5] 320334 0
4, 8, 12 weeks post change over

Eligibility
Key inclusion criteria
- Patients with stage 5 chronic kidney disease who are on haemodialysis or peritoneal dialysis, and
- with pre-existing maintenance calcitriol therapy for at least 3 months at time of recruitment, and
- have normal serum calcium level at time of recruitment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients younger than 18 years old
- Pregnant women
- Patients with hypocalcaemia or hypercalcaemia
- Patients whose serum 25-hydroxyvitamin D3 level greater than or equal to 75 nmol/L
- Patients with hypoparathyroidism or familial hypophosphataemic rickets

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The number of patients required to demonstrate a minimum of 25% of patients being able to be transferred to cholecalciferol (with 80% power; alpha 0.05) is a minimum of 26 patients. Hence, the study aims to recruit at least 30 participants.
Primary outcome is proportion of participants that can be successfully changed over to cholecalciferol from calcitriol. The success will be determined by ability of cholecalciferol to maintain albumin-corrected serum calcium level between 2.10 and 2.60 mmol/L. The success rate will be estimated using repeated-measures Poisson regression, with adjustment for confounding covariates selected by stepwise regression from the recorded baseline patient characteristics.
Secondary outcome variables for analysis include serum phosphate, intact parathyroid hormone, alkaline phosphatase, and vitamin D (25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3). These parameters will not be manipulated as part of the protocol, and differences whilst taking the different medication will be assessed using repeated measures mixed effects linear regression, adjusted for confounding covariates as above.
Baseline participant’s characteristics including age, gender, ethnicity, body mass index (BMI), smoking status, primary kidney disease(s), time on dialysis, medical comorbidities, dialysate calcium concentration, phosphate binders, pre-existing vitamin D therapy, and previous serum biomarkers will be incorporated into the analysis of the outcome variables.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
8/02/2016
Actual
Date of last participant enrolment
Anticipated
31/07/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
TAS
Recruitment hospital [1] 5053 0
Launceston General Hospital - Launceston
Recruitment postcode(s) [1] 12540 0
7250 - Launceston

Funding & Sponsors
Funding source category [1] 292698 0
Charities/Societies/Foundations
Name [1] 292698 0
Clifford Craig Medical Research Trust
Country [1] 292698 0
Australia
Primary sponsor type
Hospital
Name
Launceston General Hospital
Address
Charles St, Launceston, TAS 7250.
Country
Australia
Secondary sponsor category [1] 291473 0
University
Name [1] 291473 0
University of Tasmania
Address [1] 291473 0
Churchill Avenue, Hobart, TAS 7005
Country [1] 291473 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294181 0
Tasmanian Health and Medical Human Research Ethics Committee
Ethics committee address [1] 294181 0
Office of Research Services, University of Tasmania Hobart Campus, 301 Sandy Bay Road, Sandy Bay, TAS 7005.
Ethics committee country [1] 294181 0
Australia
Date submitted for ethics approval [1] 294181 0
19/08/2015
Approval date [1] 294181 0
18/12/2015
Ethics approval number [1] 294181 0
H0015192

Summary
Brief summary
When chronic kidney disease patients on dialysis have low calcium due to low vitamin D activity, calcitriol is the standard therapy used. However, it is costly and more likely to cause side effects of high calcium and high phosphate. On the other hand, cholecalciferol is cheaper with possibly less side effects on calcium and phosphate.
The purpose of this study is to compare cholecalciferol to calcitriol as vitamin D therapy in patients with chronic kidney disease who are on dialysis. We will change study participants who are on calcitriol to cholecalciferol, and examine cholecalciferol’s effectiveness through its effects on blood results over 12 weeks.
During recruitment, participants' age, gender, ethnicity, weight and height, smoking status, existing vitamin D therapy, kidney disease, time on dialysis, other medical conditions, dialysate calcium concentration, phosphate binders, and previous blood results will be obtained from them personally or through medical record. Baseline blood tests will be performed to analyze detailed components of the calcium and vitamin D metabolism systems. If they meet the inclusion criteria, their calcitriol therapy will be changed over to cholecalciferol. Further 3 sets of blood tests will be done at 4-week, 8-week, and 12-week period to monitor treatment effects and determine need for therapy adjustment.
We would estimate the proportion of patients on maintenance calcitriol who can be changed successfully to cholecalciferol therapy. We hypothesize that the use of cholecalciferol for maintenance therapy in adult chronic kidney disease patients on dialysis is comparable to the use of calcitriol, as shown by successful change from calcitriol to cholecalciferol therapy in a worthwhile proportion of patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62782 0
Dr Chau Wang Ng
Address 62782 0
Department of Medicine, Launceston General Hospital, Charles St, Launceston, TAS 7250.
Country 62782 0
Australia
Phone 62782 0
+61 3 6777 6777
Fax 62782 0
Email 62782 0
[email protected]
Contact person for public queries
Name 62783 0
Dr Chau Wang Ng
Address 62783 0
Department of Medicine, Launceston General Hospital, Charles St, Launceston, TAS 7250.
Country 62783 0
Australia
Phone 62783 0
+61 3 6777 6777
Fax 62783 0
Email 62783 0
[email protected]
Contact person for scientific queries
Name 62784 0
Dr Mathew C Mathew
Address 62784 0
Renal Unit, Department of Medicine, Launceston General Hospital, Charles St, Launceston, TAS 7250.
Country 62784 0
Australia
Phone 62784 0
+61 3 6777 6777
Fax 62784 0
Email 62784 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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