A Randomized Trial of Angiotensin Receptor bLocker,Fimasartan, in Aortic Stenosis (ALFA Trial)

NCT01589380 | Unknown Phase 4 DMC

• 1 other identifier: NCT16453143
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief Summary

We hypothesized that fimasartan, a new generation ARBs, would improve exercise capacity and decrease the rate of progression of AS by modifying hemodynamic factors and reducing adverse LV remodeling favorably in patients with asymptomatic moderate to severe AS.

Conditions

Critical Stenosis of Aortic Valve

Keywords

Aortic stenosis; Exercise performance; cardiopulmonary exercise test; fimasartan

Outcome Measures

Primary Outcomes (1)

• Change of VmaxO2 in Cardiopulmonary Exercise Test

  Change of VmaxO2 from baseline to 1 year follow-up. VmaxO2 is defined as the highest oxygen uptake, averaged over 5 consecutive breaths, during the last minute of symptom-limited cardiopulmonary exercise test. For each patient, the change in VamxO2 is calculated as (VmaxO2 at 1 year follow-up) - (VmaxO2 at baseline)

  Baseline and 1 year

Secondary Outcomes (13)

• Change of peak aortic jet velocity in echocardiography

  Baseline and 1 year

• Change of mean pressure gradient across aortic valve

  Baseline and 1 year

• Diastolic function - LA area (cm2), E/E' value

  Baseline and 1 year

• Left ventricular mass index (LVMI)

  Baseline and 1 year

• Development of aortic stenosis symptoms

  Baseline and 1 year

Study Arms (2)

Placebo Arm

PLACEBO COMPARATOR

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.

Drug: Placebo

Fimasartan

ACTIVE COMPARATOR

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.

Drug: Fimasartan

Interventions

Fimasartan DRUG

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.

Also known as: Fimasartan (BR-A-657; CAS : 247257-48-3; Kanarb)

Fimasartan

Placebo DRUG

Placebo was used in phase 3 clinical trial of fimasartan (NCT00922480, NCT01135212, and NCT01258673). The same placebo, which is manufactures at Boryoung pharmaceutical company, will be used in this trial. After enrollment and randomization, placebo will be administered one capsule once daily in placebo group.

Also known as: Lactose Hydrate

Placebo Arm

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Boryung Pharmaceutical Co., Ltd: collaborator
• Seoul National University Bundang Hospital: collaborator
• Severance Hospital: collaborator
• Korea University Anam Hospital: collaborator
• Korea University Guro Hospital: collaborator
• Chonnam National University Hospital: collaborator
• Samsung Medical Center: collaborator

Study Sites (7)

Chonnam University Hospital

Gwangju, Gwangju, 501-757, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul, 110-744, South Korea

RECRUITING

Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, Seoul, 135-710, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, Seoul, 136-705, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, Seoul, 136-705, South Korea

RECRUITING

Yonsei University Hospital

Seoul, Seoul, 705-717, South Korea

RECRUITING

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

fimasartan

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Yong-Jin Kim, MD,PhD

  Seoul National University Hospital

  STUDY CHAIR

• Seung-Pyo Lee, MD

  Seoul National University Hospital

  STUDY DIRECTOR

• Joo Myung Lee, MD

  Seoul National University Hospital

  STUDY DIRECTOR

• Sung-Ji Park, MD,PhD

  Samsung Medical Center, Sungkyunkwan University School of Medicine

  PRINCIPAL INVESTIGATOR

• Goo-Yeong Cho, MD,PhD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• Hyung-Kwan Kim, MD, PhD

  Seoul National University Hospital

  STUDY DIRECTOR

• Seong-Mi Park

  Korea University Anam Hospital

  PRINCIPAL INVESTIGATOR

• Seong Woo Han

  Korea University Guro Hospital

  PRINCIPAL INVESTIGATOR

• Kye Hun Kim

  Chonnam University Hospital

  PRINCIPAL INVESTIGATOR

• Geu-Ru Hong

  Yonsei University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong-Jin Kim, MD, PhD

CONTACT

82-010-3782-9382; kimdamas@snu.ac.kr

Joo Myung Lee, MD

CONTACT

82-011-9884-8439; drone80@hanmail.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 29, 2012
• First Posted: May 1, 2012
• Study Start: April 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2014
• Last Updated: May 2, 2012

Record last verified: 2012-04

Locations

KR (7)