The Effectiveness and Safety of Calcium Carbonate in Chronic Kidney Disease With Normophosphatemia

Sponsor

Indonesia University (Other)

Overall Status

Completed

CT.gov ID

NCT03550534

Collaborator

Dr Cipto Mangunkusumo General Hospital (Other)

Enrollment

Location

Arms

13.2

Actual Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background: Patient with stage 3 or 4 chronic kidney disease (CKD) usually has normal level of serum phosphate, due to increased serum fibroblast growth factor-23 (FGF23) level that resulted in increased phosphate urine excretion. On the other hand, serum FGF23 elevation was related to CKD progression, vascular calcification, cardiomegaly, and mortality. This double blind, randomized controlled trial study was conducted to evaluate effectiveness and safety of calcium carbonate administration in stage 3 or 4 CKD patients with normophosphatemia.

Hypothesis: Calcium carbonate administration is effective and safe in chronic kidney disease (CKD) with normophosphatemia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases	Drug: Calcium Carbonate Drug: Placebo oral capsule	N/A

Detailed Description

Cardiovascular disease is the most cause of mortality of chronic kidney disease (CKD) patients. As CKD progresses, the prevalence of cardiovascular disease also increased. Beside traditional cardiovascular risk factor that the investigators have known, some non-traditional cardiovascular risk factors were reported to be associated with cardiovascular disease in CKD patients, which one of them was increased level of fibroblast growth factor-23 (FGF23).[1,2]

FGF23 reduces production of 1,25-vitamin D3 and expression of sodium-phosphate cotransport, and also excretes phosphate through urine. In healthy and CKD population, increased phosphate level resulted in increased production of FGF23. Normophosphatemia state in early to moderate stage of CKD was reported due to body compensation by increasing the level of FGF23. On the other hand, increased serum FGF23 level was related to CKD progression, cardiomegaly, vascular calcification, and mortality.[1] There are several ways to prevent hyperphosphatemia, such as low phosphor intake, phosphate binder administration, and adequate dialysis.[3]

Phosphate binder was reported to give positive effects in CKD patients with hyperphosphatemia. Studies which investigated the use of phosphate binder in CKD patients with normophosphatemia to decrease FGF23 were still limited and the result was controversial.[1]

Therefore, this double blind, randomized controlled trial study investigated the effectiveness and safety of calcium carbonate in early to moderate CKD patients with normophosphatemia in lowering FGF23 levels. Study participant were randomized to receive calcium carbonate or placebo for 12 weeks. Before and after intervention, blood and urine sample were taken to examine serum FGF23, serum phosphate, urine phosphate, ionized calcium, serum calcium, urea, creatinine, estimated glomerular filtration rate (eGFR), and albumin. Effectiveness of calcium carbonate administration was indicated by serum FGF23, while safety was indicated by serum calcium.

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

The Effectiveness and Safety of Calcium Carbonate in Chronic Kidney Disease With Normophosphatemia: A Double Blind, Randomized Controlled Trial

Actual Study Start Date :

Nov 6, 2015

Actual Primary Completion Date :

Dec 11, 2016

Actual Study Completion Date :

Dec 11, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Calcium Carbonate Calcium carbonate 3 x 500 mg was given to 23 study participants for 12 weeks	Drug: Calcium Carbonate Calcium carbonate was obtained from Pharmacy Department, Faculty of Medicine, University of Indonesia. Subjects were randomized to receive calcium carbonate or placebo for 12 weeks.
Placebo Comparator: Placebo oral capsule Placebo oral capsule 3 x 1 was given to 23 study participants for 12 weeks	Drug: Placebo oral capsule Placebo oral capsule was also obtained from Pharmacy Department, Faculty of Medicine, University of Indonesia. Subjects were randomized to receive calcium carbonate or placebo for 12 weeks.

Arm

Intervention/Treatment

Experimental: Calcium Carbonate

Calcium carbonate 3 x 500 mg was given to 23 study participants for 12 weeks

Drug: Calcium Carbonate

Calcium carbonate was obtained from Pharmacy Department, Faculty of Medicine, University of Indonesia. Subjects were randomized to receive calcium carbonate or placebo for 12 weeks.

Placebo Comparator: Placebo oral capsule

Placebo oral capsule 3 x 1 was given to 23 study participants for 12 weeks

Drug: Placebo oral capsule

Placebo oral capsule was also obtained from Pharmacy Department, Faculty of Medicine, University of Indonesia. Subjects were randomized to receive calcium carbonate or placebo for 12 weeks.

Outcome Measures

Primary Outcome Measures

Serum Fibroblast Growth Factor 23 (FGF-23) [12 weeks]
Serum FGF23 (pg/ml) as cardiovascular risk factor in chronic kidney disease (CKD) was measured and compared between 2 groups before and after intervention

Secondary Outcome Measures

Serum Calcium Level [12 weeks]
Serum calcium level (mg/dl) was measured and compared between 2 groups before and after intervention

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Stage 3 or 4 chronic kidney disease patient that visit nephrology or endocrinology outpatient clinic of dr. Cipto Mangunkusumo Hospital
Normal level of serum phosphate
Agreed to join in this study