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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; Hyperphosphatemia
• Intervention / Treatment: Drug: Lanthanum Carbonate; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 2309
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Shinagawa, Tokyo, Japan, 142-0064
      • Showa University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Collaborators: Showa University School of Medicine
• Investigators: Principal Investigator: Tadao Akizawa, MD, PhD, Showa University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 24, 2011
• Primary Completion (Actual): March 25, 2019
• Study Completion (Actual): March 25, 2019

Study Registration Dates

• First Submitted: April 13, 2012
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (Estimate): April 16, 2012

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 27, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: dialysis; mortality; vascular calcification; CKD-MBD; phosphate-binder; Hemodialysis patients with hyperphosphatemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperphosphatemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Calcium-Regulating Hormones and Agents; Antacids; Calcium; Calcium Carbonate
• Other Study ID Numbers: TRIGU1111; UMIN000006815 (Registry Identifier: UMIN Clinical Trials Registry)