Low INR to Minimize Bleeding With Mechanical Valves Trial
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Warfarin.
- Who it may be relevant to
- Registry conditions: Bleeding Post-mechanical Valve Replacement, Thromboembolism Post-mechanical Valve Replacement. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Belgium, Botswana, Brazil, Cameroon, Canada +12
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical bileaflet heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.
Detailed description
Warfarin (Coumadin) is a blood thinner used to prevent blood clot formation in patients with mechanical heart valves. Blood clots can block blood flow to the brain, heart, or other parts of the body. Mechanical heart valves increases the risk of clot so patients with a mechanical heart valve must take warfarin to reduce their risk of stroke and other blood clot-related problems.
The degree to which warfarin 'works' varies from person to person, and so dosage is determined by measuring each person's response to the drug as an 'international normalized ratio' or INR. A patient with an INR over 1.0 has blood that takes longer to clot than average, and increasing INR values represent increasing time required for blood to clot. While an INR over 1.0 decreases clotting risk, it also increases bleeding risk. It is important to carefully balance these risks.
Specific INR targets have been recommended for patients with a mechanical heart valve, but these recommendations differ between scientific groups and are based on low quality evidence. Recent studies suggest that a lower INR target range than is currently recommended can be used safely. A laboratory study showed that warfarin effectively prevents blood clot formation on mechanical heart valves as long as the INR is 1.5 or above. Two moderately-sized clinical studies showed that an INR target range of 1.5-2.5 resulted in less bleeding than the usual higher target range without increasing blood clot formation or stroke in patients with a newer valve model. Whether we could use a lower INR target range for patients with a mechanical aortic valve remains controversial.
This study evaluates the use of a lower INR target (1.5 to 2.5) in patients with a mechanical bileaflet heart valve in the aortic position. This study will inform physicians about whether a lower INR target will decrease the risk of bleeding or increase the risk of blood clot formation and stroke. These results have the potential to reduce the burden of bleeding in patients with a mechanical heart valve who require lifelong warfarin (Coumadin) treatment.
Interventions
- Drug Warfarin
Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.
Primary outcome measures
- Thrombosis/thromboembolism [Time frame: Through study completion, an expected mean of 2-3 years]
- Major bleeding [Time frame: Through study completion, an expected mean of 2-3 years]
Secondary outcome measures (12)
- All cause mortality [Time frame: Through study completion, an expected mean of 2-3 years]
- All clinically important bleeding [Time frame: Through study completion, an expected mean of 2-3 years]
- Minor bleeding [Time frame: Through study completion, an expected mean of 2-3 years]
- All stroke [Time frame: Through study completion, an expected mean of 2-3 years]
- Ischemic stroke [Time frame: Through study completion, an expected mean of 2-3 years]
- Hemorrhagic stroke [Time frame: Through study completion, an expected mean of 2-3 years]
- Type 1, 2 or 3 myocardial infarction [Time frame: Through study completion, an expected mean of 2-3 years]
- Systemic thromboembolism [Time frame: Through study completion, an expected mean of 2-3 years]
- Valve thrombosis [Time frame: Through study completion, an expected mean of 2-3 years]
- Pulmonary embolism [Time frame: Through study completion, an expected mean of 2-3 years]
- Deep vein thrombosis [Time frame: Through study completion, an expected mean of 2-3 years]
- New renal replacement therapy [Time frame: Through study completion, an expected mean of 2-3 years]
Eligibility criteria
Inclusion criteria
- Age is 18 or older at the time of enrolment
- Have had a bileaflet mechanical heart valve implant in the aortic position 3 or more months ago
- Written informed consent from either the patient or substitute decision maker
Exclusion criteria
- Has a second implanted mechanical valve (any position)
- Lower boundary of planned INR range is less than 2.0
- Pregnant or expecting to become pregnant during the study follow-up
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Brazil · 5 centers
- Sociedade Hospitalar Angelina Caron — Campina Grande do Sul
- HEW Cardiologia LTDA — Joinville
- InCor-HCFMUSP — Cerqueira César
- Fundação Universitária de Cardiologia mantededora do Instituto de Cardiologia e Transplant — Brasília
- Dante Pazzanese Institute of Cardiology — São Paulo
Canada · 5 centers
- Nova Scotia Health Authority — Halifax
- Hamilton General Hospital — Hamilton
- London Health Sciences Centre Research Inc. — London
- The Ottawa Hospital Research Institute — Ottawa
- Jewish General Hospital — Montreal
Belgium · 4 centers
- Ziekenhuis Oost-Limburg — Genk
- AZ Oostende — Ostend
- Imelda Hospital — Keerbergen
- Universitair Ziekenhuis Leuven — Leuven
Denmark · 3 centers
- Esbjerg & Grindsted Hospital - University Hospital of Southern Denmark — Esbjerg
- Southern Jutland Hospital — Aabenraa
- Aarhus University Hospital — Aarhus
Nepal · 3 centers
- Shahid Gangalal National Heart Centre — Kathmandu
- Nobel Medical College and Teaching Hospital — Biratnagar
- BP Koirala Institute of Health Sciences — Dharān
United Kingdom · 3 centers
- Golden Jubilee National Hospital — Clydebank
- Liverpool Heart & Chest Hospital — Liverpool
- South Tees Hospitals NHS Foundation Trust of The James Cook University Hospital — Middlesbrough
Italy · 2 centers
- Città di Lecce Hospital — Lecce
- Azienda Ospedaliero Universitaria Policlinico Riuniti Foggia — Foggia
Botswana · 1 center
- University of Botswana, at Princess Marina Hospital — Gaborone
Cameroon · 1 center
- St. Elizabeth Catholic General Hospital — Kumbo
China · 1 center
- Fuwai Hospital, CAMS & PUMC — Beijing
Germany · 1 center
- Universitätsklinikum Jena — Jena
Netherlands · 1 center
- Erasmus University Medical Centre — Rotterdam
Pakistan · 1 center
- Shifa Clinical Research Center — Islamabad
Russia · 1 center
- Meshalkin National Medical Research Center — Novosibirsk
Saudi Arabia · 1 center
- King Faisal Specialist Hospital & Research Centre — Riyadh
South Korea · 1 center
- Soonchunhyang University Gumi Hospital — Gumi
Spain · 1 center
- Hospital de la Santa Creu i Sant Pau — Barcelona
Publications
- Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. PMID 24512654
- Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, De Feo M, Amarelli C, Sasso FC, Salvatore T, Ellison GM, Indolfi C, Cotrufo M, Nappi G. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial. Am Heart J. 2010 Jul;160(1):171-8. doi: 10.1016/j.ahj.2010.05.005. PMID 20598989
Identifiers
NCT: NCT03636295 · 5139