A Trial of Fimasartan for Early Diastolic Heart Failure (FINE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Asan Medical Center
Sponsor:
Collaborator:
Boryung Pharmaceutical Co., Ltd
Information provided by (Responsible Party):
Duk-Hyun Kang, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01691118
First received: September 20, 2012
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

Approximately half of hypertensive patients have diastolic dysfunction and diastolic dysfunction is associated with development of congestive heart failure and increased mortality. Although diastolic heart failure associated with hypertension is a clinically significant problem, few clinical trials have been conducted and there is no proven pharmacological therapy to improve outcomes. To the best of the investigators knowledge, there has been no randomized trial to demonstrate that an antihypertensive drug improves diastolic function in hypertensive patients with diastolic dysfunction. The investigators hypothesize that fimasartan added to standard therapy will be superior to placebo in improving diastolic dysfunction in mildly symptomatic patients with hypertension and diastolic dysfunction, and try to examine this hypothesis in a double-blind, randomized comparison study using echocardiography.


Condition Intervention Phase
Hypertension
Drug: Fimasartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Fimasartan for Improvement of Diastolic Dysfunction in Hypertensive Patients

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Change in E/E' ratio [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Change in the ratio of E velocity (Early mitral inflow velocity) to E' velocity (Early mitral annular velocity) from baseline to 10 months follow-up.


Secondary Outcome Measures:
  • Change in BNP levels [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Change in BNP levels from baseline to 10 months follow-up.

  • Change in left ventricular mass [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Change in LV mass from baseline to 10 months follow-up.

  • Change in left atrial volume [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Change in left atrial volume from baseline to 10 months follow-up.

  • Change in global left ventricular strain [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Change in global left ventricular strain from baseline to 10 months follow-up.

  • Change in functional class [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Change in New York Heart Association (NYHA) functional class from baseline to 10 months follow-up.

  • Change in clinical composite [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
    The clinical composite assessment is based on a change in the NYHA functional class and occurrences of serious adverse events (SAE). Patients with an improvement in NYHA class and without SAE are classified as improved, and those as aggravated if they have SAE during treatment or report worsening of their NYHA class at the endpoint visit.


Estimated Enrollment: 128
Study Start Date: September 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fimasartan
Fimasartan 60mg qd for 10 months.
Drug: Fimasartan
Placebo Comparator: Placebo

Detailed Description:

Approximately half of hypertensive patients have diastolic dysfunction and diastolic dysfunction is associated with development of congestive heart failure and increased mortality. The Framingham study reported that 51% of patients with HF have a preserved left ventricular (LV) ejection fraction and hypertension is the strongest risk factor for HF with preserved ejection fraction, also termed diastolic heart failure. The rates of death and morbidity in these patients are as high as in patients with HF and a low LV ejection fraction. Hypertensive patients are at increased risk of developing LV hypertrophy and myocardial fibrosis, which cause relaxation abnormality and decreased compliance of LV with a rise in the LV diastolic pressure. Although HF associated with hypertension is a clinically significant problem, few clinical trials have been conducted and there is no proven pharmacological therapy to improve outcomes.

Because the activation of rennin-angiotensin-aldosterone system (RAAS) has been shown to induce LV hypertrophy and myocardial fibrosis, the RAAS may play a central role in the pathogenic process from hypertension to diastolic HF. Inhibitors of RAAS have been considered as a treatment option for these patients, and the angiotensin receptor blockers (ARB) have been of interest because they antagonize the effects of angiotensin II more completely. The largest clinical trial, the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE), recently reported that treatment with irbesartan did not reduce the risk of death or hospitalization for cardiovascular causes among 4,128 patients who had HF with a preserved LV ejection fraction. The negative result observed in the I-PRESERVE trial may have been the consequence of the following possible factors. First, this trial may have targeted patients in whom the disease process was too advanced for ARBs to be effective. Second, irbesartan may not be an appropriate ARB for a HF trial, because ARBs are not all the same in terms of clinical outcome data in patients with HF. Irbesartan did not have outcome data on reducing HF hospitalization in high-risk hypertensive patients and telmisartan showed no benefits compared to placebo in these patients, although candesartan and valsartan significantly reduced endpoint in placebo-controlled trials. Telmisartan and irbesartan have PPARγ activity and this activity might neutralize the beneficial effects of ARB on HF, because it is well known that PPARγ agonist, rosiglitazone, increases the incidences of HF significantly.

Evaluating the effect of treatments on diastolic dysfunction has been limited by difficulties in non-invasive measure of LV diastolic pressure, but recent advances in echocardiography have made it possible to assess diastolic dysfunction accurately and reproducibly. Thus, additional clinical studies with the other ARBs are needed in hypertensive patients with diastolic dysfunction and assessment of diastolic function by echocardiography will be helpful to determine whether addition of ARB to standard therapy is beneficial to hypertensive patients with diastolic dysfunction. Fimasartan is the first ARB developed in Korea, and was felt to be particularly appropriate for examining the hypothesis that the ARB can improve diastolic dysfunction associated with hypertension, because fimasartan is a potent and well-tolerated ARB. To the best of our knowledge, there has been no randomized trial to demonstrate that an antihypertensive drug improves diastolic function in hypertensive patients with diastolic dysfunction. We hypothesize that fimasartan added to standard therapy will be superior to placebo in improving diastolic dysfunction in mildly symptomatic patients with hypertension and diastolic dysfunction, and try to examine this hypothesis in a double-blind, randomized comparison study using echocardiography.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Untreated hypertension: systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg or Treated hypertension
  • Current heart failure symptoms with NYHA class II
  • Evidence of diastolic dysfunction showing any 2 of the following:

E/E' > 10, LV posterior wall thickness > 11 mm, BNP level > 40 pg/mL

Exclusion Criteria:

  • Planned cardiac surgery or planned major non-cardiac surgery within the study period
  • Stroke or coronary revascularization in the past 6 months
  • LV ejection fraction < 50%
  • Hypertrophic or restrictive cardiomyopathy, moderate or severe valve disease, constrictive pericarditis
  • Atrial fibrillation with a heart rate > 120/min
  • Sitting systolic BP < 100 mmHg
  • Sitting systolic BP > 160 mmHg or diastolic BP > 95 mmHg despite antihypertensive therapy
  • Significant renal disease manifested by serum creatinine > 2.5 mg/dL
  • Clinically significant pulmonary disease, coronary artery disease
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691118

Contacts
Contact: Duk-Hyun Kang, MD, PhD 82-2-3010-3166 dhkang@amc.seoul.kr
Contact: Byung Joo Sun, MD 82-2-3010-1540 lionheart@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Duk Hyun Kang, MD, PhD    82-2-3010-3166    dhkang@amc.seoul.kr   
Contact: Byung Joo Sun, MD    82-2-301-1540    lionheart@amc.seoul.kr   
Principal Investigator: Duk Hyun Kang, MD, PhD         
Sponsors and Collaborators
Asan Medical Center
Boryung Pharmaceutical Co., Ltd
Investigators
Principal Investigator: Duk-Hyun Kang, MD, PhD Asan Medical Center
  More Information

No publications provided

Responsible Party: Duk-Hyun Kang, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01691118     History of Changes
Other Study ID Numbers: 2012-0229
Study First Received: September 20, 2012
Last Updated: May 20, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
Hypertension
Angiotensin Receptor Blocker
Diastolic Dysfunction

Additional relevant MeSH terms:
Hypertension
Heart Failure, Diastolic
Vascular Diseases
Cardiovascular Diseases
Heart Failure
Heart Diseases
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014