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Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial
BACKGROUND: Warfarin is an oral anticoagulant medication that disrupts the liver’s production of clotting factors. While this medication is highly effective for the prevention of thromboembolic events, it also has a narrow therapeutic range and a vulnerability to interactions with other drugs and vi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973068/ https://www.ncbi.nlm.nih.gov/pubmed/27488365 http://dx.doi.org/10.1186/s13063-016-1516-9 |
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author | Heran, Balraj S. Allan, G. Michael Green, Lee Korownyk, Christina Kolber, Michael Olivier, Nicole Flesher, Mary Garrison, Scott |
author_facet | Heran, Balraj S. Allan, G. Michael Green, Lee Korownyk, Christina Kolber, Michael Olivier, Nicole Flesher, Mary Garrison, Scott |
author_sort | Heran, Balraj S. |
collection | PubMed |
description | BACKGROUND: Warfarin is an oral anticoagulant medication that disrupts the liver’s production of clotting factors. While this medication is highly effective for the prevention of thromboembolic events, it also has a narrow therapeutic range and a vulnerability to interactions with other drugs and vitamin K-containing foods. Warfarin is commonly ingested at dinnertime, the same time of day that dietary vitamin K consumption (found largely in green leafy vegetables) is most variable. While the long half-life of warfarin might make this irrelevant, the ultra short half-life of vitamin K and the possibility of a hepatic first-pass effect for warfarin make it worth evaluating whether morning ingestion of warfarin, when vitamin K levels are consistently low, leads to greater stability of its anticoagulant effect. An examination of the timing of administration on the effectiveness of warfarin has never before been conducted. METHODS/DESIGN: This is a 7-month Prospective Randomized Open Blinded End-point (PROBE) study in which established evening warfarin users (primary care managed Canadian outpatients in the provinces of British Columbia and Alberta) will be randomized to either switch to morning ingestion of warfarin (the intervention) or to continue with evening use (the control). The primary outcome is the percent change in the proportion of time spent outside the therapeutic range of the international normalized ratio (INR) blood test. Secondary outcomes include change in proportion of time spent within the therapeutic INR range (TTR), percentage of patients with TTR >75 %, percentage of patients with TTR <60 %, and major warfarin-related cardiovascular events (including all-cause mortality, hospitalization for stroke, hospitalization for GI bleeding, and deep venous thrombosis/pulmonary embolism). We will also compare whether day-to-day variability in the consumption of high vitamin K-containing foods at baseline affects the baseline TTR in this cohort of evening warfarin users. DISCUSSION: This study addresses whether the timing of warfarin ingestion influences the stability of its anticoagulant effect. Should morning ingestion prove superior, the safety and effectiveness of this medication, and hence the prevention of stroke, pulmonary embolus, and major hemorrhage, could potentially be improved with no added cost or inconvenience to the patient. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02376803. Registered on 25 February 2015. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1516-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4973068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49730682016-08-05 Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial Heran, Balraj S. Allan, G. Michael Green, Lee Korownyk, Christina Kolber, Michael Olivier, Nicole Flesher, Mary Garrison, Scott Trials Study Protocol BACKGROUND: Warfarin is an oral anticoagulant medication that disrupts the liver’s production of clotting factors. While this medication is highly effective for the prevention of thromboembolic events, it also has a narrow therapeutic range and a vulnerability to interactions with other drugs and vitamin K-containing foods. Warfarin is commonly ingested at dinnertime, the same time of day that dietary vitamin K consumption (found largely in green leafy vegetables) is most variable. While the long half-life of warfarin might make this irrelevant, the ultra short half-life of vitamin K and the possibility of a hepatic first-pass effect for warfarin make it worth evaluating whether morning ingestion of warfarin, when vitamin K levels are consistently low, leads to greater stability of its anticoagulant effect. An examination of the timing of administration on the effectiveness of warfarin has never before been conducted. METHODS/DESIGN: This is a 7-month Prospective Randomized Open Blinded End-point (PROBE) study in which established evening warfarin users (primary care managed Canadian outpatients in the provinces of British Columbia and Alberta) will be randomized to either switch to morning ingestion of warfarin (the intervention) or to continue with evening use (the control). The primary outcome is the percent change in the proportion of time spent outside the therapeutic range of the international normalized ratio (INR) blood test. Secondary outcomes include change in proportion of time spent within the therapeutic INR range (TTR), percentage of patients with TTR >75 %, percentage of patients with TTR <60 %, and major warfarin-related cardiovascular events (including all-cause mortality, hospitalization for stroke, hospitalization for GI bleeding, and deep venous thrombosis/pulmonary embolism). We will also compare whether day-to-day variability in the consumption of high vitamin K-containing foods at baseline affects the baseline TTR in this cohort of evening warfarin users. DISCUSSION: This study addresses whether the timing of warfarin ingestion influences the stability of its anticoagulant effect. Should morning ingestion prove superior, the safety and effectiveness of this medication, and hence the prevention of stroke, pulmonary embolus, and major hemorrhage, could potentially be improved with no added cost or inconvenience to the patient. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02376803. Registered on 25 February 2015. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1516-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-04 /pmc/articles/PMC4973068/ /pubmed/27488365 http://dx.doi.org/10.1186/s13063-016-1516-9 Text en © Heran et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol Heran, Balraj S. Allan, G. Michael Green, Lee Korownyk, Christina Kolber, Michael Olivier, Nicole Flesher, Mary Garrison, Scott Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial |
title | Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial |
title_full | Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial |
title_fullStr | Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial |
title_full_unstemmed | Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial |
title_short | Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial |
title_sort | effect of medication timing on anticoagulation stability in users of warfarin (the inrange rct): study protocol for a randomized controlled trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973068/ https://www.ncbi.nlm.nih.gov/pubmed/27488365 http://dx.doi.org/10.1186/s13063-016-1516-9 |
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