Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Background and study aims
Oral anticoagulant (blood thinning) drugs are very useful for treating and preventing blood clots. However, with them comes a risk of bleeding if the blood gets too “thin” (too slow to clot). Currently, warfarin is the most commonly used drug for treating/preventing blood clots, however dosages must be closely monitored as it can cause several severe side effects, such as making people more prone to bleeding. A new generation of anticoagulant drugs have become available which are believed to be safer than warfarin. It is already known that people who eat little vitamin K (a vitamin mainly found in green leafy vegetables which plays a key role in blood clotting), are very sensitive to the blood-thinning effect of warfarin. However, it is unknown whether these people would also more sensitive to the new drugs. Tests in animals have shown that those with little vitamin K in their diets were more sensitive to the new drugs, however as yet, no one has checked whether this is the same in humans. This study is looking at whether the blood-thinning activity of two new drugs (dabigatra and rivaroxaban) is influenced by how much vitamin K we eat.

Who can participate?
Thirty patients over the age of 65 suspected of even little vitamin K and thirty patients under the age of 65 with healthy, balanced diets.

What does the study involve?
All participants are asked to complete a questionnaire about the foods that they have eaten over the last week. A sample of blood is then taken through a vein which is tested in the laboratory for vitamin K levels and how much clotting factor is present (proteins that control bleeding) so that the clotting time between the two groups of patients can be compared.

What are the possible benefits and risks of participating?
There are no direct benefits involved for those taking part in this study. There is a small risk of pain, bruising or bleeding during and after blood samples are taken.

Where is the study run from?
Royal Victoria Infirmary (Newcastle)

When is the study starting and how long is it expected to run for?
September 2013 to April 2018

Who is funding the study?
NIHR Newcastle Biomedical Research Centre (UK)

Who is the main contact?
Professor Farhad Kamali

Trial website

Contact information



Primary contact

Prof Farhad Kamali


Contact details

Institute of Cellular Medicine
Newcastle University
Newcastle upon Tyne
United Kingdom
+44 191 208 8043

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Investigation of the effect of vitamin K deficiency on anticoagulant response to novel oral anticoagulants (direct thrombin inhibitors and FXa inhibitors) ex-vivo



Study hypothesis

Vitamin K deficiency enhances anticoagulation response to new generation of oral anticoagulants.

Ethics approval

NRES Committee North East- Newcastle & North Tyneside 2, 18/05/2016, ref: 12/NE/0209

Study design

Single-centre observational cohort study

Primary study design


Secondary study design

Cohort study

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.


Anticoagulation response


The study will recruit 30 subjects suspected of low dietary vitamin K intake (elderly inpatients not on warfarin), 30 elderly medically stable subjects (inpatients not on warfarin) with healthy diets, and 30 healthy younger subjects with adequate dietary vitamin K intake.

All subjects will complete a validated simple questionnaire (FFQ) which records their food intake of vitamin K containing foods on average and over the past week. A sample of 20 ml fasting venous blood is then taken for later laboratory tests Plasma fasting vitamin K levels will be measured as an indication of subjects’ dietary status. Activated partial thromboplastin time (aPTT), prothrombin time (PT) and modified PT will be measured in plasma incubated with rivaroxaban (100-500ng/ml). The kinetics of thrombin formation in plasma in the presence of drug will be determined using the endogenous thrombin potential (ETP) test.

Intervention type



Not Applicable

Drug names


Primary outcome measure

Clotting time

Secondary outcome measures

No secondary outcome measures

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Older subjects:
1. >65 years old
2. Medically stable
3. Without liver dysfunction
4. Able to give informed consent
5. Suspected of vitamin K deficiency as evaluated by the use of dietary questionnaire

Younger subjects:
1. <65 years of age
2. Healthy
3. Having a normal healthy diet as evaluated by the dietary questionnaire

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Less than 18 years of age
2. Liver dysfunction
3. Receiving anticoagulation therapy

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Infirmary
Victoria Road
Newcastle upon Tyne
United Kingdom

Sponsor information


Newcastle upon Tyne Hospitals Foundation Trust

Sponsor details

Royal Victoria Infirmary
Newcastle upon Tyne
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

NIHR Newcastle Biomedical Research Centre

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Research output (publications, conferences and presentations), and educational materials for patients and health professionals involved in anti-coagulation management, including GPs and hospital doctors.

Intention to publish date


Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes