Clinical trial NCT01578200: Outcome Study of Lanthanum Carbonate Compared With Calcium Carbonate in Hemodialysis Patients : Landmark Study
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemodialysis
Hyperphosphatemia
Keywords: CKD-MBD
phosphate-binder
vascular calcification
mortality
dialysis
Hemodialysis patients with hyperphosphatemia
Lead sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Sponsor class: OTHER
Collaborators: name: Showa University School of Medicine
First posted: 2012-04-16
Enrollment: 2309
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiovascular event free survival time.
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
measure: Secondary hyperparathyroidism free survival
timeFrame: 3 years
measure: Hip fracture free survival
timeFrame: 3 years
measure: Quality of life questionnaire (KDQOL-SF, v1.3)
timeFrame: 3 years
measure: Bone mineral density (DEXA)
timeFrame: 3 years
Other outcomes:
Locations:
city: Shinagawa
country: Japan
facility: Showa University
state: Tokyo
Study officials:
affiliation: Showa University
name: Tadao Akizawa, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ogata H, Fukagawa M, Hirakata H, Kagimura T, Fukushima M, Akizawa T; LANDMARK Investigators and Committees. Effect of Treating Hyperphosphatemia With Lanthanum Carbonate vs Calcium Carbonate on Cardiovascular Events in Patients With Chronic Kidney Disease Undergoing Hemodialysis: The LANDMARK Randomized Clinical Trial. JAMA. 2021 May 18;325(19):1946-1954. doi: 10.1001/jama.2021.4807.