Outcome Study of Lanthanum Carbonate Compared With Calcium Carbonate in Hemodialysis Patients : Landmark Study (LANDMARK)
Primary Purpose
Hemodialysis, Hyperphosphatemia
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Lanthanum Carbonate
Calcium Carbonate
Sponsored by
About this trial
This is an interventional treatment trial for Hemodialysis focused on measuring CKD-MBD, phosphate-binder, vascular calcification, mortality, dialysis, Hemodialysis patients with hyperphosphatemia
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
Sites / Locations
- Showa University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Lanthanum carbonate
Calcium Carbonate
Arm Description
Patients are given Lanthanum Carbonate oral administration after meals three times per day in total daily dose of 750-2250mg.
Patients are given Calcium carbonate oral administration after meals three times per day in total daily dose of 3.0g.
Outcomes
Primary Outcome Measures
Cardiovascular event free survival time.
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
Secondary hyperparathyroidism free survival
Hip fracture free survival
Quality of life questionnaire (KDQOL-SF, v1.3)
Bone mineral density (DEXA)
Full Information
NCT ID
NCT01578200
First Posted
April 13, 2012
Last Updated
November 27, 2020
Sponsor
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Collaborators
Showa University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01578200
Brief Title
Outcome Study of Lanthanum Carbonate Compared With Calcium Carbonate in Hemodialysis Patients : Landmark Study
Acronym
LANDMARK
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
December 24, 2011 (undefined)
Primary Completion Date
March 25, 2019 (Actual)
Study Completion Date
March 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Collaborators
Showa University School of Medicine
4. Oversight
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemodialysis, Hyperphosphatemia
Keywords
CKD-MBD, phosphate-binder, vascular calcification, mortality, dialysis, Hemodialysis patients with hyperphosphatemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2309 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lanthanum carbonate
Arm Type
Experimental
Arm Description
Patients are given Lanthanum Carbonate oral administration after meals three times per day in total daily dose of 750-2250mg.
Arm Title
Calcium Carbonate
Arm Type
Active Comparator
Arm Description
Patients are given Calcium carbonate oral administration after meals three times per day in total daily dose of 3.0g.
Intervention Type
Drug
Intervention Name(s)
Lanthanum Carbonate
Intervention Type
Drug
Intervention Name(s)
Calcium Carbonate
Primary Outcome Measure Information:
Title
Cardiovascular event free survival time.
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
3 years
Title
Secondary hyperparathyroidism free survival
Time Frame
3 years
Title
Hip fracture free survival
Time Frame
3 years
Title
Quality of life questionnaire (KDQOL-SF, v1.3)
Time Frame
3 years
Title
Bone mineral density (DEXA)
Time Frame
3 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tadao Akizawa, MD, PhD
Organizational Affiliation
Showa University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Showa University
City
Shinagawa
State/Province
Tokyo
ZIP/Postal Code
142-0064
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
34003226
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.
Results Reference
derived
Learn more about this trial
Outcome Study of Lanthanum Carbonate Compared With Calcium Carbonate in Hemodialysis Patients : Landmark Study
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