UMIN-CTR Clinical Trial

Basic information
Public title	Prevention of incident fracture of Osteoporosis in Japan(Multi-center Randomized Trial with Risedronate and VitaminK2)
Acronym	Japanese Osteoporosis Intervention Trial -03 (JOINT-03)
Scientific Title	Prevention of incident fracture of Osteoporosis in Japan(Multi-center Randomized Trial with Risedronate and VitaminK2)
Scientific Title:Acronym	Japanese Osteoporosis Intervention Trial -03 (JOINT-03)
Region	Japan

Condition
Condition	Osteoporosis
Classification by specialty	Endocrinology and Metabolism Geriatrics Obsterics and gynecology Orthopedics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To confirm the clinical significance of concurrent use of vitaminK2 to risedronate by incident vertebral fracture rate and incident nonvertebral fracture rate as index
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	Incident vertebral fracture rate and incident nonvertebral fracture rate
Key secondary outcomes	Bone mineral density,stature,QOL, undercarboxylated osteocalcin,safety

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Risedronate(2 years)
Interventions/Control_2	Risedronate +vitaminK2(2 years)
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	65 years-old <=
Age-upper limit	Not applicable
Gender	Female
Key inclusion criteria	1.Criteria for initiation of pharmacotherapy to prevent fragility fracture(Japanese Guidelines for the prevention and treatment of osteoporosis 2006 edition) 2.Age>=65 years old(female) 3.Risk factor number for incident fracture>=1(in A-TOP research group) 4.Possible to walk alone 5.Possible to answer QOL questionnaire
Key exclusion criteria	1.Using warfarin 2.Secondary osteoporosis and low bone mass disease except osteoporosis 3.Having contraindication in using drugs 4.Hypothyroidism and hyperparathyroidism 5.Disfunction of communication of the intention 6.Prevalent vertebral fracture>=6 7.Deformation of vertebra 8.Abnormal heart function,abnormal hepatic function,abnormal kidney function 9.Taken bisphosphonate within previous 6 months
Target sample size	1820

Research contact person
Name of lead principal investigator	1st name Hajime Middle name Last name Orimo
Organization	Japan Osteoporosis Foundation
Division name	President
Zip code	1030011
Address	2-14, Nihonbashi-odenmatyo, Tyuo-ku, Tokyo, Japan
TEL	03-5640-1841
Email	info@jpof.or.jp

Public contact
Name of contact person	1st name Yoji Middle name Last name Mitadera
Organization	Public health research foundation
Division name	CSP-A-TOP
Zip code	1690051
Address	1-1-7,Nishiwaseda,Shinjuku-ku,Tokyo,Japan
TEL	03-5287-2638
Homepage URL	http://www.a-top.jp/
Email	a-top@csp.or.jp

Sponsor
Institute	Japan Osteoporosis Society/A-TOP consortium
Institute
Department

Funding Source
Organization	Public health research foundation
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	-
Address	-
Tel	-
Email	-

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2008 Year 02 Month 01 Day

Related information
URL releasing protocol	http://www.a-top.jp/
Publication of results	Unpublished

Result
URL related to results and publications	https://link.springer.com/article/10.1007/s00774-016-0768-5
Number of participants that the trial has enrolled	1983
Results	Concurrent treatment with vitamin K2 and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.
Results date posted	2021 Year 05 Month 26 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2016 Year 08 Month 02 Day
Baseline Characteristics	The baseline characteristics of the patients in the FAS were well balanced between the two groups. The mean age of the patients was 75.3 years. About 54 % of patients had BMD less than YAM - 3 SD and about 70% of patients did not receive osteoporosis treatment during past 1 year. Half of patients had ucOC level less than 4.5 ng/mL.
Participant flow	A total of 1983 patients from 123 institutes in Japan were randomized and 931 patients in the risedronate and vitamin K2 group and 943 in the risedronate alone group were included the FAS after excluding those who did not receive treatment and those who were not eligible.
Adverse events	Adverse events occurred in 80 patients (83 reports) in the risedronate and vitamin K2 group and in 52 patients (54 reports) in the risedronate alone group. All adverse drug reactions were known and the most common adverse drug reactions were gastrointestinal disorders (4.05% in the risedronate and vitamin K2 group and 2.56% in the risedronate alone group). Serious adverse events occurred in 14 patients (14 reports) including 7 patients who died in the risedronate and vitamin K2 group and in 16 patients (16 reports) including 12 patients who died in the risedronate alone group and the included 3 adverse drug reactions (2 patients in the risedronate and vitamin K2 group and 1 patient in the risedronate alone group).
Outcome measures	The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2007 Year 11 Month 02 Day
Date of IRB	2007 Year 11 Month 02 Day
Anticipated trial start date	2008 Year 01 Month 01 Day
Last follow-up date	2011 Year 12 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2017 Year 06 Month 30 Day

Other
Other related information

Management information
Registered date	2008 Year 01 Month 22 Day
Last modified on	2021 Year 06 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001194