Clinical trial NCT06409533: Rate Control Efficacy in Atrial Fibrillation With Rheumatic Mitral Stenosis: Lenient vs Strict Rate Control Strategies
Official title: Rate Control Efficacy in Atrial Fibrillation With Rheumatic Mitral Stenosis: Assessing Clinical Outcomes of Lenient Versus Strict Heart Rate Control in Reducing Hospitalizations, Improving Quality of Life, and Enhancing Functional Capacity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Rheumatic Mitral Stenosis
Arrhythmias, Cardiac
Keywords: Atrial Fibrillation
Mitral Stenosis
Rheumatic Heart Disease
Heart Rate Control
Rate Control
Lead sponsor: University of Brawijaya
Sponsor class: OTHER
Collaborators: name: Saiful Anwar Hospital
First posted: 2024-05-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if different types of heart rate control work to improve the clinical outcomes of patients with atrial fibrillation related to rheumatic mitral stenosis in terms of reducing hospitalizations, improving quality of life, and enhancing physical functional capacities. The two types of heart rate (HR) control are strict (resting HR of 60-80 bpm) versus lenient (resting HR of 81-110 bpm) rate control strategies. The main questions it aims to answer are:

* Can lenient versus strict heart rate control reduce rehospitalization in patients with atrial fibrillation and rheumatic mitral stenosis?
* Does lenient versus strict heart rate control improve the quality of life (QoL) in patients with atrial fibrillation and rheumatic mitral stenosis?
* Does lenient versus strict heart rate control enhance functional capacity in patients with atrial fibrillation and rheumatic mitral stenosis?

Researchers will compare strict rate control to lenient rate control to see if a particular rate control strategy is non-inferior to the other.

Participants will:

* Take standardized drugs as per PERKI (Indonesian Heart Association) guidelines for Atrial Fibrillation, which would be either beta-blockers, digoxin, or in combination. This standardized treatment of Atrial Fibrillation will be monitored once every month to see if the dose needs to be titrated in order to reach targeted heart rate control.
* After the target of HR control is reached, the participant will be followed up every two weeks via telephone to check for any signs and symptoms.
* Furthermore, after the HR target is reached, the participant will visit the cardiology outpatient clinics once every month for 3 consecutive months to see the clinical outcomes of hospitalization, QoL via SF-36 questionnaire, and functional capacities with 6MWT (6-minute walk test).
* Additionally, the cardiac function would be evaluated by echocardiography at the baseline (time of enrollment) and at the end of the follow up period.

Detailed description: Rheumatic Heart Disease (RHD) often begins with untreated Group A Streptococcal infections leading to acute rheumatic fever and potentially progressing to Mitral Stenosis (MS), a condition characterized by the narrowing of the mitral valve that disrupts normal blood flow and increases atrial pressure. This pathology is closely associated with Atrial Fibrillation (AF), the most common arrhythmia in patients with MS, affecting 30-40% of such patients, with prevalence increasing with age and disease duration. The management of AF in this group focuses on anticoagulation to prevent thromboembolic events and heart rate control through medications like beta-blockers and digitalis to improve symptoms and cardiac efficiency.

Despite the guidance provided by the Rate Control Efficacy in Permanent Atrial Fibrillation (RACE II) trial, which showed non-inferiority of lenient rate control (resting heart rate \<110 bpm) compared to strict control (resting heart rate \<80 bpm) in reducing cardiovascular morbidity and mortality, no studies have specifically explored these strategies in patients with AF and rheumatic MS. This research gap underscores the importance of our study, aiming to assess the safety and efficacy of lenient versus strict rate control in this distinct clinical subset, potentially offering critical insights that could lead to optimized, personalized treatment protocols for these high-risk patients.

The objective of this clinical trial is to evaluate the effectiveness of different heart rate control strategies in improving clinical outcomes for patients with atrial fibrillation associated with rheumatic mitral stenosis. The outcomes of interest include reducing hospitalizations, enhancing quality of life, and improving functional capacities within three months follow-up period. The study compares two heart rate control strategies: strict control, with a target resting heart rate of 60-80 beats per minute (bpm), and lenient control, with a target resting heart rate of 81-110 bpm. The primary research questions are:

* Can lenient versus strict heart rate control reduce rehospitalization in patients with atrial fibrillation and rheumatic mitral stenosis?
* Does lenient versus strict heart rate control improve quality of life in these patients?
* Does lenient versus strict heart rate control enhance their functional capacity?

To determine whether one strategy is non-inferior to the other, researchers will compare strict and lenient rate control outcomes. Participants will:

* Receive standardized pharmacological treatment according to the PERKI (Indonesian Heart Association) guidelines for Atrial Fibrillation, potentially including beta-blockers, digoxin, or a combination thereof. This treatment regimen will be monitored monthly to adjust dosages and achieve the targeted heart rate.
* Once the target heart rate is achieved, participants will undergo bi-weekly telephone follow-ups to monitor for any signs and symptoms.
* Additionally, after reaching the heart rate target, participants will attend monthly follow-up visits at the cardiology outpatient clinic for three consecutive months to assess clinical outcomes, including hospitalization rates, quality of life via the SF-36 questionnaire, and functional capacity using the 6-minute walk test (6MWT).
* Cardiac function will be evaluated through echocardiography at the time of enrollment and at the end of the follow-up period.

The study has been approved by Health Research Ethics Committee from the main hospital (Saiful Anwar Hospital) and the satellite hospitals, i.e. Dr. Iskak Regional General Hospital and Prima Husada Sukorejo Hospital. The participants and the outcome assessors will be blinded to ensure the objectiveness, whereas the care providers would oversee the standardized treatments and heart rate control targets.

Eligibility criteria: Inclusion Criteria:

* Participants with atrial fibrillation and moderate-to-severe rheumatic mitral stenosis, as confirmed by ECG and echocardiography and diagnosed by the attending cardiologist.
* Patients with atrial fibrillation and severe rheumatic mitral stenosis who are ineligible for surgical intervention.
* Mean resting heart rate \> 80 bpm, with or without the use of rate control medication.
* Age range between 18 and 80 years.
* Provision of informed consent by participants.

Exclusion Criteria:

* Patients with paroxysmal atrial fibrillation.
* Heart failure (HF) with unstable hemodynamics.
* HF classified as NYHA (New York Heart Association) class IV.
* Patients currently undergoing treatment for hyperthyroidism who have been euthyroid for \< 3 months.
* Individuals diagnosed with a stroke, either ischemic or hemorrhagic.
* Symptomatic bradycardia accompanied by AV (atrioventricular) conduction disturbances.
* Use of a pacemaker, implantable cardioverter-defibrillator (ICD), or undergoing cardiac resynchronization therapy (CRT).
* Diagnosis of malignancy or obstructive sleep apnea (OSA).
* Patients with congenital heart defects.
* Atrial fibrillation secondary to electrolyte disturbances, hyperthyroidism, or reversible/non-cardiac causes.
* Inability to perform daily physical activities.
* Patients who have undergone CABG (coronary artery bypass graft), cardiac surgery, or a heart transplant within the past three months.

Primary outcomes:
measure: Number of Hospitalizations
timeFrame: 0-3 months
measure: Quality of Life as Measured by the Short Form-36 (SF-36) Questionnaire
timeFrame: 3 months
measure: Functional Capacity as Measured by 6-Minutes Walk Test (6MWT)
timeFrame: 3 months
Secondary outcomes:
measure: Change of Quality of Life as Measured by the Short Form-36 (SF-36) Questionnaire
timeFrame: 0-3 months
measure: Change of Functional Capacity as Measured by 6-Minutes Walk Test (6MWT)
timeFrame: 0-3 months
measure: Change of Metabolic Equivalents (METs) as Estimated from 6-Minutes Walk Test (6MWT)
timeFrame: 0-3 months
measure: Change of VO2max as Estimated from 6-Minutes Walk Test (6MWT)
timeFrame: 0-3 months
Other outcomes:
Locations:
city: Malang
country: Indonesia
facility: Saiful Anwar Hospital
state: East Java
city: Pasuruan
country: Indonesia
facility: Prima Husada Sukorejo Hospital
state: East Java
city: Tulung Agung
country: Indonesia
facility: Dr. Iskak Regional General Hospital
state: East Java
Study officials:
affiliation: University of Brawijaya
name: Ardian Rizal, MD, FIHA
role: PRINCIPAL_INVESTIGATOR
References: