Pharmacy and Poisons Board
Protocol No: ECCT/25/04/04 Date of Protocol: 14-06-2023
Study Title:

A Low INR to Minimize bleeding with mechanical valves Trial (LIMIT)
Study Objectives:

The objectives are to evaluate the safety and efficacy of a common, lower INR target range in patients with bileaflet aortic mechanical valves.
Laymans Summary:

The heart has four valves: aortic, mitral, pulmonary, and tricuspid. When these valves are affected by disease, it results in valvular heart disease. This condition impacts a portion of the population, though exact numbers in Africa or Kenya are unknown. However, it's estimated to affect about 2.5% of people in high-income countries. Valvular heart disease can range from mild to severe. Mild cases are often managed with medication, but as symptoms worsen, the disease is categorized as moderate or severe. Severe symptomatic valve disease typically requires surgical intervention.

 
Mechanical heart valves are commonly used devices for treating severe valve disease. Patients with mechanical heart valves need blood thinners to prevent clot formation. Warfarin is the most commonly used blood thinner, and it works by interfering with Vitamin K. To ensure the correct level of blood thinning, a test called the INR (international normalized ratio) is used. Maintaining the INR within a specific range is crucial: insufficient thinning can lead to clots, while excessive thinning can cause bleeding. For patients with mechanical aortic valves, the recommended INR range is often between 2.5 and 3.5, which comes with an increased risk of bleeding. Lowering the INR target range could potentially prevent blood clots while reducing the risk of bleeding.
 
Our study aims to determine if maintaining a lower INR range (1.5 to 2.5) is as safe and effective as the current guidelines in preventing blood clots and reducing bleeding in people with a mechanical aortic valve. Approximately 30 to 50 centers will participate in this study, enrolling a total of 2,625 participants. The Karen Hospital will recruit participants from our satellite clinics, the main hospital, and through medical camps. Participants will be randomly assigned to either the lower INR target group (1.5 to 2.5) or the current practice group. Eligible participants must be at least 18 years old, have a bileaflet mechanical heart valve implant in the aortic position at least 3 months prior, and must provide written informed consent. Those who plan to become pregnant, are pregnant, have another mechanical valve, or have a planned INR level less than 2 will not be enrolled.
 
Although participants and the study team will know the assigned groups, professionals reviewing safety information, such as bleeding or clotting incidents, will remain unaware of the groups. All participants will be followed up during routine clinic visits, with at least 10 INR tests conducted each year. Follow-up visits will monitor for illnesses and assess overall well-being, continuing until 131 clot-related events have occurred.
 
Participation in the study is voluntary, and participants can withdraw at any time. All participants will be closely monitored and treated if they experience any side effects or health issues, regardless of their group.
 
Abstract of Study:

Introduction:

 
Valvular heart disease is linked to significant morbidity and mortality, often necessitating surgery to replace damaged heart valves with mechanical or bioprosthetic valves. Mechanical valves are preferred for their durability, but they require lifelong anticoagulant therapy with vitamin K antagonists as the only approved treatment. Maintaining correct INR levels is crucial, as bleeding in this group has been associated with poorer prognosis. This trial aims to evaluate the safety and efficacy of maintaining a lower INR level between 1.5 and 2.5.
 
Study Setting: This study will enroll approximately 2,625 participants across 30 to 50 sites globally.
 
Study Design:
 
This is a prospective, randomized, open-label, blinded end-point (PROBE), multicenter clinical trial. The intervention of interest is a low INR target range (1.5 to 2.5) compared to the current guideline-recommended practice.
 
Expected Results:
 
Previous studies suggest that lower INR targets may reduce the risk of bleeding while maintaining protection against thromboembolic events. We expect to obtain similar results.