Trial Outcomes & Findings for Vitamin K Supplementation in Post-Menopausal Osteopenia (NCT NCT00150969)

NCT ID: NCT00150969

Last Updated: 2023-12-28

Results Overview

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 440 participants
• Primary outcome timeframe: 0 to 24 months
• Results posted on: 2023-12-28

Participant Flow

recruitment from January 2002 to September 2006 through health fairs, community posters and advertisements.

453 participants signed consent. 13 were not included in analysis(10 screen failure,3 drop out at baseline)

Participant milestones

Measure	Phyloquinone 5 mg Vitamin K1	Placebo dummy pill identicle to vitamin k
24 Month Main Study STARTED	217	223
24 Month Main Study COMPLETED	198	202
24 Month Main Study NOT COMPLETED	19	21
24-48 Month Extension STARTED	121	140
24-48 Month Extension COMPLETED	33	40
24-48 Month Extension NOT COMPLETED	88	100

Reasons for withdrawal

Measure	Phyloquinone 5 mg Vitamin K1	Placebo dummy pill identicle to vitamin k
24 Month Main Study Adverse Event	3	4
24 Month Main Study Death	1	1
24 Month Main Study Lack of Efficacy	1	8
24 Month Main Study Lost to Follow-up	3	2
24 Month Main Study Protocol Violation	4	2
24 Month Main Study Withdrawal by Subject	7	4
24-48 Month Extension Withdrawal by Subject	6	5
24-48 Month Extension Lack of Efficacy	0	1
24-48 Month Extension Adverse Event	1	3
24-48 Month Extension Other Reason	81	91

Baseline Characteristics

Vitamin K Supplementation in Post-Menopausal Osteopenia

Baseline characteristics by cohort

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1	Placebo n=223 Participants dummy pill identicle to vitamin k	Total n=440 Participants Total of all reporting groups
Age, Continuous	58.9 years n=93 Participants	59.2 years n=4 Participants	59.0 years n=27 Participants
Sex: Female, Male Female	217 Participants n=93 Participants	223 Participants n=4 Participants	440 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: 0 to 24 months

Population: For our 2 year BMD anlayses we included all 440 women based on intention to treat using last observation carried forward for missing data.

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=223 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.	-1.28 percentage change in BMD Standard Deviation 3.5 • Interval -0.67 to 0.54	-1.22 percentage change in BMD Standard Deviation 3.0 • Interval -0.67 to 0.54

PRIMARY outcome

Timeframe: 0 to 24 months

Population: For our 2 year BMD anlayses we included all 440 women based on intention to treat using last observation carried forward for missing data.

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=223 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.	-0.69 percentage change in BMD Standard Deviation 2.8 • Interval -0.37 to 0.75	-0.88 percentage change in BMD Standard Deviation 3.2 • Interval -0.37 to 0.75

SECONDARY outcome

Timeframe: 0 to 24 months

Population: For our 2 year BMD anlayses we included all 440 women based on intention to treat using last observation carried forward for missing data.

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=223 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.	-1.47 percentage change in BMD Standard Deviation 3.7	-1.83 percentage change in BMD Standard Deviation 3.5

SECONDARY outcome

Timeframe: 0 to 24 months

Population: For our 2 year BMD anlayses we included all 440 women based on intention to treat using last observation carried forward for missing data.

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=221 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.	-2.49 percentage change in BMD Standard Deviation 4.0	-2.55 percentage change in BMD Standard Deviation 4.7

SECONDARY outcome

Timeframe: 0-24 months

measured by osteocalcin on elecsys platform

Outcome measures

Measure	Phyloquinone n=198 Participants 5 mg Vitamin K1 daily	Placebo n=192 Participants dummy pill identicle to vitamin k
Effect of Vitamin K1 Supplementation on Levels of Bone Formation Marker	21 ng/ml Standard Deviation 7.3	24 ng/ml Standard Deviation 7.5

SECONDARY outcome

Timeframe: 0-24 months

measured by CTX Elisa assay on elecsys platform

Outcome measures

Measure	Phyloquinone n=192 Participants 5 mg Vitamin K1 daily	Placebo n=198 Participants dummy pill identicle to vitamin k
Effect of Vitamin K1 Supplementation on Level of Bone Resorption Markers (C-telopeptide: CTX)	0.58 ng/ml Standard Deviation 0.21	0.54 ng/ml Standard Deviation 0.21

SECONDARY outcome

Timeframe: 0 to 24 months

measured by osteocalcin hydroxyapatite binding assay

Outcome measures

Measure	Phyloquinone n=192 Participants 5 mg Vitamin K1 daily	Placebo n=198 Participants dummy pill identicle to vitamin k
Effect of Vitamin K1 Supplementation on Percent of Carboxylation of Osteocalcin	-21.4 percentage of undercarboxylated OC Standard Deviation 10.3	-2.0 percentage of undercarboxylated OC Standard Deviation 6.8

SECONDARY outcome

Timeframe: 0 to 48 months

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=33 Participants 5 mg Vitamin K1 daily	Placebo n=40 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Total Hip Between Treatment Arms.	-1.39 percentage change in BMD Standard Deviation 3.6	-1.52 percentage change in BMD Standard Deviation 4.5

SECONDARY outcome

Timeframe: 0 to 48 months

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=33 Participants 5 mg Vitamin K1 daily	Placebo n=40 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Lumbar Spine (L1-L4) Between Treatment Arms.	-0.40 percentage change in BMD Standard Deviation 4.7	-1.76 percentage change in BMD Standard Deviation 3.8

SECONDARY outcome

Timeframe: 0 to 48 months

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=33 Participants 5 mg Vitamin K1 daily	Placebo n=40 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Femoral Neck Between Treatment Arms.	-2.05 percentage change in BMD Standard Deviation 4.3	-2.71 percentage change in BMD Standard Deviation 4.8

SECONDARY outcome

Timeframe: 0 to 48 months

BMD was measured yearly on one scanner at UHN using DEXA Hologic 4500A densitometer

Outcome measures

Measure	Phyloquinone n=33 Participants 5 mg Vitamin K1 daily	Placebo n=40 Participants dummy pill identicle to vitamin k
Percent Change in Bone Mineral Density (BMD) at the Ultra-distal Radius Between Treatment Arms.	-5.35 percentage change in BMD Standard Deviation 5.1	-5.23 percentage change in BMD Standard Deviation 4.5

SECONDARY outcome

Timeframe: up to 48 months

These include hospitalizations for pneumonia, heart failure, gastro-intestinal bleeding, elective and non-elective surgery, cancer and death.

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=223 Participants dummy pill identicle to vitamin k
Difference in Serious Adverse Events	15 events	25 events

SECONDARY outcome

Timeframe: up to 48 months

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=223 Participants dummy pill identicle to vitamin k
Difference in Number of New Cancers by Treatment Arm.	3 events	12 events

SECONDARY outcome

Timeframe: up to 48 months

these included fragility fractures

Outcome measures

Measure	Phyloquinone n=217 Participants 5 mg Vitamin K1 daily	Placebo n=223 Participants dummy pill identicle to vitamin k
Difference in Number of New Clinical Fractures by Treatment Arm.	11 events	21 events

Adverse Events

Phyloquinone

Serious events: 15 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 25 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phyloquinone n=217 participants at risk 5 mg Vitamin K1	Placebo n=223 participants at risk dummy pill identicle to vitamin k
General disorders hospitalization	5.1% 11/217 • Number of events 13 • Adverse event data was collected for the entire study period of 48 months	5.8% 13/223 • Number of events 16 • Adverse event data was collected for the entire study period of 48 months
General disorders Cancer	1.4% 3/217 • Number of events 3 • Adverse event data was collected for the entire study period of 48 months	4.9% 11/223 • Number of events 12 • Adverse event data was collected for the entire study period of 48 months
General disorders Death	0.46% 1/217 • Number of events 1 • Adverse event data was collected for the entire study period of 48 months	0.45% 1/223 • Number of events 4 • Adverse event data was collected for the entire study period of 48 months

Other adverse events

Measure	Phyloquinone n=217 participants at risk 5 mg Vitamin K1	Placebo n=223 participants at risk dummy pill identicle to vitamin k
Gastrointestinal disorders nausea and vomitting	5.1% 11/217 • Number of events 11 • Adverse event data was collected for the entire study period of 48 months	4.5% 10/223 • Number of events 10 • Adverse event data was collected for the entire study period of 48 months

Additional Information

Dr. Angela M Cheung

University Health Network

Phone: 416-340-4841

Email: jscher@uhnresearch.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place