Effect of Losartan on the Neurohumoral Axis and Ventricular Remodeling of Patients With Severe Aortic Regurgitation Undergoing Valve Surgery
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change of NT-proBNP during the first 3 months after aortic valve surgery in patients with severe aortic regurgitation.
研究概览
简要总结
Why Is This Study Important? The heart has valves that help control blood flow. Aortic regurgitation (AR) is a condition where one of these valves (the aortic valve) doesn't close properly, causing blood to leak back into the heart. Over time, this makes the heart work harder and grow larger (remodeling) to keep up. Many patients with severe AR need valve replacement surgery to fix this problem.
After surgery, the heart doesn't have to work as hard, and over time, it can shrink back to a healthier size (reverse remodeling). However, doctors don't know if medications can help speed up or improve this healing process. This study aims to find out if a common blood pressure medication, losartan, can help the heart recover better after surgery.
What Do the Investigators Already Know? Doctors often prescribe medications like ACE inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and spironolactone to people with heart failure because these drugs help the heart function better and prevent worsening disease. However, these medications haven't been studied in people with valve disease because most major research studies excluded patients with valve problems.
Even though there is not strong evidence, many doctors prescribe these medications after valve surgery, assuming they might be helpful. But is that really the case? That's the question this study hopes to answer.
What Is This Study About?
This study will test whether losartan, a medication often used for high blood pressure, can help hearts recover better after aortic valve replacement surgery. The researchers will compare two groups of patients:
- One group will take losartan (50 mg per day) after surgery.
- The other group will take a placebo (a pill with no active medication).
By comparing these two groups, the study will determine whether losartan helps the heart shrink back to a normal size faster and function better after surgery.
How Will the Study Work? Who? 60 patients with severe AR who are having aortic valve replacement surgery.
How? Patients will be randomly placed into one of the two groups (losartan or placebo).
For how long? Patients will be followed for one year after surgery. What Will Be Measured?
Doctors will check patients four times: before surgery, and 1 month, 3 months, and 12 months after surgery. At each visit, the investigators will measure:
- NT-proBNP levels: A blood test that tells us how much strain the heart is under. Lower levels mean the heart is recovering well.
- Echocardiogram: An ultrasound of the heart to check its size and function.
- 6-minute walk test: To see if patients feel stronger and can exercise better.
- Quality of life survey: To understand how patients feel physically and emotionally.
- Kidney function and electrolyte levels: To check for medication side effects.
Why Is This Study Exciting? This is the first study to test whether a medication can help the heart heal better after valve surgery. If losartan proves beneficial, it could change how doctors treat patients after surgery and lead to better recovery, stronger hearts, and healthier lives.
Many people with aortic regurgitation have to wait until their symptoms get worse before patients can have surgery. If this study finds that medication can speed up healing, it could help doctors treat valve disease more effectively and improve long-term outcomes for patients.
What Happens Next? If losartan is found to be helpful, this study could lead to larger research trials and, eventually, new treatment guidelines for people who have had aortic valve surgery. If it doesn't help, doctors will know not to prescribe it unnecessarily, preventing unnecessary side effects and costs for patients. Either way, the results will help improve care for people with heart valve disease.
By participating in this study, patients are helping researchers discover new ways to improve heart health and recovery after surgery.
详细描述
Pharmacological therapy targeting the neurohumoral axis have emerged as the cornerstone of Heart Failure (HF) treatment. The angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), spironolactone, beta-blockers and neprilysin inhibitors act on the neurohumoral axis, having prognostic impact with proven benefits in terms of ventricular remodeling, morbidity and mortality. However, these drugs have not been tested in the context of valvular cardiomyopathy, as pivotal studies excluded patients with valve disease. There are robust evidences that medical treatment does not reduce mortality in the preoperative phase of valve disease, acting only on symptom management. However, in the period after valve surgery, there is absence of data regarding benefit of medical therapy focused on the neurohumoral axis. Aortic regurgitation represents a condition characterized by pronounced ventricular remodeling during the asymptomatic phase, often developing significant reverse remodeling after surgery. Consequently, it presents as a very interesting model for studying the impact of renin-angiotensin-aldosterone system inhibition after valve intervention. Currently, clinicians frequently precribe drugs targeting the neurohumoral axis in the postoperative phase for these patients, extrapolating from findings in classical HF studies. However, there is no evidence in the literature for this approach, which is common in clinical practice. Therefore, this study aims to assess the impact of the use of the ARB losartan on neurohumoral remodeling in the postoperative period of patients with aortic regurgitation undergoing valve surgery, measuring NT-proBNP, a natriuretic peptide strongly associated with ventricular remodeling. The primary objective of the study is to compare NT-proBNP values in patients taking losartan 50 mg/day versus placebo in the first 3 months after aortic valve replacement for severe aortic regurgitation. This is a pilot, randomized, double-blind clinical study with a sample of 60 patients, who will be randomized in a 1:1 ratio. Patients in both arms will be assessed at 4 time points: randomization, 1, 3 and 12 months after surgery, undergoing a 6-minute walk test and Short-Form Health Survey (SF-36v2) quality of life questionnaire, laboratory tests including NT-proBNP, electrolytes and renal function, as well as a complete echocardiographic evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •To avoid potential bias in data interpretation, the following patients will be excluded:
- •Those who underwent cardiac surgery in the context of cardiogenic shock or infective endocarditis;
- •Patients with ischemic cardiomyopathy;
- •Patients with other significant concomitant valvular diseases.
- •Patients with conditions where losartan use may be harmful will also be excluded, including:
- •Chronic kidney disease with an estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m²);
- •Systolic blood pressure (SBP) < 90 mmHg at the time of randomization;
- •Elevated serum potassium (K > 5.5 mEq/L) at the time of randomization;
- •Pregnancy;
- •Known intolerance or allergy to losartan.
研究组 & 干预措施
Losartan group
losartan 50 mg/day
干预措施: Losartan 50 mg (Drug)
placebo group
placebo group
干预措施: Placebo (Drug)
结局指标
主要结局
Change of NT-proBNP during the first 3 months after aortic valve surgery in patients with severe aortic regurgitation.
时间窗: 3 months
The primary outcome of the study will be to evaluate the reduction of NT-proBNP during the first 3 months after aortic valve surgery in patients with severe aortic regurgitation.
次要结局
- Evaluation of the effects of losartan on quality of life after aortic valve surgery in 1, 3 and 12 months.(1, 3 and 12 months)
- Evaluation of the effects of losartan on major cardiovascular events after aortic valve surgery in 1, 3 and 12 months.(1, 3 and 12 months)
- Evaluation of the effects of losartan on kidney function after aortic valve surgery in 1, 3 and 12 months.(1, 3 and 12 months)
- Evaluation of the effects of losartan on NT-proBNP levels after aortic valve surgery in 1 and 12 months.(12 months)
- Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.(1, 3, and 12 months)
- Evaluation of the effects of losartan on functional capacity after aortic valve surgery in 1, 3 and 12 months(1, 3 and 12 months)
研究者
Vitor Emer Egypto Rosa
Principal investigator
University of Sao Paulo General Hospital