A Randomized Trial of Angiotensin Receptor bLocker,Fimasartan, in Aortic Stenosis (ALFA Trial) (ALFA)
Critical Stenosis of Aortic Valve
About this trial
This is an interventional treatment trial for Critical Stenosis of Aortic Valve focused on measuring Aortic stenosis, Exercise performance, cardiopulmonary exercise test, fimasartan
Eligibility Criteria
Inclusion Criteria:
- Male or female
- Age: 20-75 years
- Moderate to severe aortic stenosis defined as a continuous wave Doppler determined peak aortic valve jet velocity of 3.0 - 4.5 m/s, mean pressure gradient of 25 - 49 mmHg, or aortic valve area of 0.76 - 1.5 cm2.
- Asymptomatic aortic stenosis patients, Stationary or minimum dyspnea on exertion (NYHA Fc ≤ I or II) will be included.
- Patients who were prescribed ACEI or ARBs for treatment of hypertension will be enrolled after 2 weeks wash-out period.
- SBP 120-140 mmHg with or without medication regardless of presence of hypertension or not.
- Patients with BP > 140/90 mmHg with or without medication will be included after their BP is controlled with anti-hypertensive medication other than ACEI/ARBs.
- Patients who are able to perform appropriate cardiopulmonary exercise test with treadmill.
- The patient agrees to the study protocol and the schedule of clinical, cardiopulmonary exercise test, and echocardiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site.
Exclusion Criteria:
- Symptomatic aortic stenosis: presence of exertional dyspnea (≥ NYHA Fc III), angina or syncope
- Very severe aortic stenosis regardless of presence of symptoms. It was defined as a critical stenosis in the aortic valve area ≤ 0.75 cm2 accompanied by a peak aortic jet velocity ≥4.5 m/s or a mean transaortic pressure gradient ≥50 mm Hg on Doppler echocardiography.
- Uncontrolled HTN (SBP > 160 or DBP >100) without ACEI or ARBs during 2-weeks wash out period in patients who were prescribed ACEI or ARBs for treatment of hypertension.
- Patients with known history of coronary artery disease including myocardial infarction, regardless of the treatment (medication only, percutaneous coronary intervention, or coronary artery bypass grafting).
- Planned cardiac surgery or planned major non-cardiac surgery within the study period.
- Stroke or resuscitated sudden death in the past 6 months.
- Chronic disease requiring treatment with oral, intravenous, or intra-articular corticosteroids (use of topical, or nasal corticosteroids is permissible).
- Untreated hyperthyroidism or hypothyroidism with TSH levels more than 2 times upper limit of normal.
- A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer.
- Female of child-bearing potential who do not use adequate contraception and women who are pregnant or breast-feeding.
- Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.
- Evidence of congestive heart failure, or left ventricular ejection fraction < 50%.
- Significant renal disease manifested by serum creatinine > 2.0mg/dL
- Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal).
- Documented bilateral renal artery stenosis or known contraindication of ACEI or ARBs
- History of chronic obstructive pulmonary disease or asthma manifested by acute aggravation of COPD in the past 6 months, or currently taking bronchodilators including long-acting beta2 agonist, anticholinergics, or inhaled steroids.
- Other valvular disease : Moderate or severe mitral regurgitation or mitral stenosis, Moderate or severe aortic regurgitation
- Patients who are unable to perform cardiopulmonary exercise test.
- Unwillingness or inability to comply with the procedures described in this protocol.
- Patient who have been diagnosed with galactose intolerance, lactase deficiency, malabsorption of glucose or galactose which is main ingredient of placebo.
Sites / Locations
- Seoul National University Bundang HospitalRecruiting
- Chonnam University HospitalRecruiting
- Seoul National University HospitalRecruiting
- Samsung Medical Center, Sungkyunkwan University School of MedicineRecruiting
- Korea University Anam HospitalRecruiting
- Korea University Guro HospitalRecruiting
- Yonsei University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Active Comparator
Placebo Arm
Fimasartan
Placebo: Capsule that is containing lactate hydrate, identically appearing with fimasartan will be administered to patient in placebo group, once daily. Same placebo drug which was used in phase 3 clinical trial of fimasartan will be provided by Boryoung Phamaceutical company. Dose titration will be done with same criteria of fimasartan group. 30mg form and 60 mg form of placebo will be identical in its morphology.
Fimasartan, Initial dose will be started with 30mg per day. At 12 months follow-up after the enrollment, dose titration up to 60 mg per day will be made with target blood pressure of 120/80. Dose escalization from 30mg/day to 60mg/day will be performed in the case of follow-up systolic blood pressure is over 120. If the follow-up systolic blood pressure is less than 120, initial dose of 30mg/day will be maintained throughout the study duration. If hypotension (BP < 90/60) is developed, the study medication will be discontinued and the patient will be included safety outcome analysis and intention to treat analysis. Per protocol analysis will be also performed. The dose of placebo will be adjusted identically, according to the blood pressure criteria of fimasartan.