The objective in the vanguard phase of the LIMIT trial is to assess the feasibility of recruiting 400 subjects over approximately 3 years at 5 centres. The objectives in the full trial are to evaluate the safety and efficacy of a common, lower INR…
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the incidence of major bleeding.
Secondary outcome
The most important secondary outcome is all thrombosis/thromboembolism
(composite of ischemic stroke, systemic thromboembolism, valve thrombosis).
Other secondary outcomes include:
1) All-cause mortality (selected rather than cardiovascular mortality, as
cause-specific mortality is often difficult to ascertain or define in complex
cardiovascular patients in whom multi-end-organ dysfunction may accompany
cardiovascular decline)
2) All bleeding
3) Minor bleeding
4) All stroke
5) Ischemic stroke
6) Hemorrhagic stroke
7) Type 1, 2 or 3 myocardial infarction
8) Systemic thromboembolism
9) Valve thrombosis
10) Pulmonary embolism
11) Deep vein thrombosis
12) New renal replacement therapy
13) Time in therapeutic range
14) Proportion of patients with extreme INR values (>4)
Background summary
A vitamin K antagonist 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 increase
the risk of blood clots so patients with a mechanical heart valve must take a
vitamin K antagonist to reduce their risk of stroke and other blood
clot-related problems.
The degree to which a vitamin K antagonists '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 are 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.
The purpose of this research is to find out if a lower INR target range (1.5 to
2.5) results in lower rates of bleeding when compared to the current guideline
recommended INR target, in patients with mechanical valves. The study will
also confirm that a lower target INR maintains adequate protection against
blood clots.
Study objective
The objective in the vanguard phase of the LIMIT trial is to assess the
feasibility of recruiting 400 subjects over approximately 3 years at 5 centres.
The objectives in the full trial are to evaluate the safety and efficacy of a
common, lower INR target range in patients with bileaflet aortic mechanical
valves
Study design
The LIMIT trial is a prospective, randomized, open-label, blinded end-point,
multicenter clinical trial.
Intervention
All enrolled patients will already be taking a VKA according to typical care.
The intervention group will receive a dose titrated to achieve an INR target of
1.5 to 2.5. The control group will receive a dose titrated to achieve the
current guideline recommended INR range. Oral VKA dosage and INR frequency
monitoring will be under the direction of the local anticoagulation clinic. We
will mandate at least 10 INR measurements per year or at minimum (a 6 week
specific dosing algorithm or INR monitoring schedule).
Study burden and risks
For patients who are allocated to the lower INR target range, the risk of
developing a blood clot may be increased. Blood clots may dislodge from the
site they develop and travel to other parts of the body, where they have the
potential to block blood flow and cause stroke, heart attack, or gut or limb
ischemia. However, based on previous studies that observed no increased risk of
blood clot formation in patients assigned to a lower INR target range, we
believe this risk is very small.
Patients may or may not benefit directly from participating in this study. If
their INR target range is lowered as part of the study, it may reduce the risk
of bleeding.
Bar 237
Hamilton L8L 2X2
CA
Bar 237
Hamilton L8L 2X2
CA
Listed location countries
Age
Inclusion criteria
1) Have had a bileaflet mechanical heart valve implant in the aortic position
>=3 months ago,
2) Be >=18 years of age at the time of enrolment,
3) Provide written informed consent (either from the patient or a substitute
decision-maker).
Exclusion criteria
1) Have a second implanted mechanical valve (any position),
2) Lower boundary of planned INR range is less than 2.0,
3) Pregnant or expecting to become pregnant during the study follow-up.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004975-37-NL |
| ClinicalTrials.gov | NCT036362 |
| CCMO | NL78645.078.21 |