LANDMARK: Outcome Study of Lanthanum Carbonate Compared With Calcium Carbonate in Hemodialysis Patients : Landmark Study

Sponsor

Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan (Other)

Overall Status

Completed

CT.gov ID

NCT01578200

Collaborator

Showa University School of Medicine (Other)

2,309

Enrollment

Location

Arms

Duration (Months)

26.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate decrease in cardiovascular mortality and morbidity in Japanese hemodialysis patients treated with Lanthanum carbonate compared with those with Calcium carbonate.

Condition or Disease	Intervention/Treatment	Phase
Hemodialysis Hyperphosphatemia	Drug: Lanthanum Carbonate Drug: Calcium Carbonate	Phase 3

Detailed Description

Elevated serum phosphate and calcium in dialysis patients are independently associated with increased risk of arterial calcification and mortality. Calcium-based phosphate binders can induce hypercalcaemia and are associated with progression of vascular calcification. A recent randomized study demonstrated that sevelamer, a non-calcium-based phosphate binders, reduced mortality in elderly hemodialysis patients compared with calcium-based phosphate binders. Lanthanum carbonate is another efficacious and well-tolerated non-calcium phosphate binder. A post-hoc survival analysis of lanthanum carbonate versus standard therapy suggested a survival benefit of lanthanum carbonate treatment for elderly patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

2309 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Outcome Study of Lanthanum Carbonate Compared With Calcium Carbonate on Cardiovascular Mortality and Morbidity in Patients With Chronic Kidney Disease on Hemodialysis (CKD5D)

Study Start Date :

Dec 24, 2011

Actual Primary Completion Date :

Mar 25, 2019

Actual Study Completion Date :

Mar 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lanthanum carbonate Patients are given Lanthanum Carbonate oral administration after meals three times per day in total daily dose of 750-2250mg.	Drug: Lanthanum Carbonate
Active Comparator: Calcium Carbonate Patients are given Calcium carbonate oral administration after meals three times per day in total daily dose of 3.0g.	Drug: Calcium Carbonate

Arm

Intervention/Treatment

Experimental: Lanthanum carbonate

Patients are given Lanthanum Carbonate oral administration after meals three times per day in total daily dose of 750-2250mg.

Drug: Lanthanum Carbonate

Active Comparator: Calcium Carbonate

Patients are given Calcium carbonate oral administration after meals three times per day in total daily dose of 3.0g.

Drug: Calcium Carbonate

Outcome Measures

Primary Outcome Measures

Cardiovascular event free survival time. [3 years]
Cardiovascular event consisting of death due to cardiovascular diseases including sudden cardiac death (ICD-10 codes R96.0/96.1), nonfatal myocardial infarction, nonfatal cerebral stroke including transient ischemic attack, TIA, unstable angina, hospitalization for heart failure, hospitalization for ventricular arrhythmia

Secondary Outcome Measures

Overall survival [3 years]
Secondary hyperparathyroidism free survival [3 years]
Hip fracture free survival [3 years]
Quality of life questionnaire (KDQOL-SF, v1.3) [3 years]
Bone mineral density (DEXA) [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

hemodialysis patients with hyperphosphatemia who require phosphate binders
hemodialysis for more than 3 months
patients who have at least one calcification risk factor (elderly > 65 years, postmenopausal woman, type 2 diabetes mellitus)
intact-PTH < or = 240pg/mL
life expectancy > 1 year
with written informed consent

Exclusion Criteria:

contraindications to lanthanum carbonate and calcium carbonate
swallowing disorders
severe GI disorders
history of obstructed bowels
history of IHD/stroke within 6 months before randomization
NYHA classification Ⅲ-Ⅳ
severe liver dysfunction (AST or ALT greater than 3 times the upper limit of institution
require treatment of arrhythmia
severe malnutrition
malignancy of any type within the last five years
peritoneal dialysis patients
pregnant or possibly pregnant women or women on lactation and planned to get pregnant within study term
ineligible patients according to the investigator's judgment