Effect of Losartan on the Neurohumoral Axis and Ventricular Remodeling of Patients With Severe Aortic Regurgitation Undergoing Valve Surgery.

NCT07099859 | Recruiting Phase 4

• 2 other identifiers: 81900224.0.0000.00682023/15710-5
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Valve Diseases; Left Ventricle Remodeling; Aortic Regurgitation Disease; Heart Failure Congestive; Natriuretic Peptide, Brain

Keywords

aortic regurgitation; valve disease; heart surgery; heart failure; losartan; Brain natriuretic peptide - BNP; biomarkers; renin-angiotensin-aldosterone system; neurohumoral axis

Outcome Measures

Primary Outcomes (1)

• Change of NT-proBNP during the first 3 months after aortic valve surgery in patients with severe aortic regurgitation.

  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.

  3 months

Secondary Outcomes (11)

• 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 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 functional capacity 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

Study Arms (2)

Losartan group

EXPERIMENTAL

losartan 50 mg/day

Drug: Losartan 50 mg

placebo group

PLACEBO COMPARATOR

placebo group

Drug: Placebo

Interventions

Losartan 50 mg DRUG

Losartan 50 mg per day

Losartan group

Placebo DRUG

Placebo 1 pill per day

placebo group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• Postoperative period of aortic valve replacement surgery due to severe aortic regurgitation of any etiology;
• Signed Informed Consent Form.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vitor Emer Egypto Rosa: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (1)

Heart Institute of the School of Medicine of the University of São Paulo

São Paulo, São Paulo, 05403-000, Brazil

RECRUITING

Related Publications (16)

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MeSH Terms

Conditions

Heart Valve Diseases; Ventricular Remodeling; Heart Failure; Aortic Valve Insufficiency

Interventions

Losartan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Aortic Valve Disease

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Vitor E. E. Rosa, MD, PhD

  Heart Institute of the School of Medicine of the University of São Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vitor E. E. Rosa, MD, PhD

CONTACT

551126613653; vitor.rosa@hc.fm.usp.br

Mariana P Lopes, MD

CONTACT

551126611548; mari.pezzutelopes@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Model Details: 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.

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: August 1, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

BR (1)