Heart Valve DiseasesPhase 4ARBNPNCT07099859
Effect of Losartan on the Neurohumoral Axis and Ventricular Remodeling of Patients With Severe Aortic Regurgitation Undergoing Valve Surgery.
A Phase 4 study testing Losartan 50 mg in people with Heart Valve Diseases and Left Ventricle Remodeling, run by Vitor Emer Egypto Rosa at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Valve Diseases, Left Ventricle Remodeling, Aortic Regurgitation Disease
- What is being tested?
- Losartan 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Jul 2025to 1 Jul 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years;
- Postoperative period of aortic valve replacement surgery due to severe aortic regurgitation of any etiology;
- Signed Informed Consent Form.
Who cannot join
- 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);
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Heart Institute of the School of Medicine of the University of São Paulo
São Paulo, São Paulo, 05403-000
COMISSÃO CIENTIFICA INCOR, 551126614158, ccientifica@incor.usp.br
Anna L Lopes, 551126615504, ccientifica@incor.usp.br
About this study
Official title: Effect of Losartan on the Neurohumoral Axis and Ventricular Remodeling of Patients With Severe Aortic Regurgitation Undergoing Valve Surgery
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Heart Valve Diseases, Left Ventricle Remodeling, Aortic Regurgitation Disease, Heart Failure Congestive, Natriuretic Peptide, Brain
- Being tested
- Losartan 50 mg, Placebo
- Keywords
- aortic regurgitation, valve disease, heart surgery, heart failure, losartan, Brain natriuretic peptide - BNP, biomarkers, renin-angiotensin-aldosterone system, neurohumoral axis
- Medical subject headings
- Heart Valve Diseases, Ventricular Remodeling, Heart Failure, Aortic Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losartan 50 mgDrug
Losartan 50 mg per day
PlaceboDrug
Placebo 1 pill per day
| Study group | Role | What they receive |
|---|---|---|
| Losartan group | Experimental | losartan 50 mg/day Receives: Drug: Losartan 50 mg |
| placebo group | Placebo comparator | placebo group Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (11)
Evaluation of the effects of losartan on NT-proBNP levels after aortic valve surgery in 1 and 12 months.
-NT-proBNP (pg/ml) reduction at 1 and 12 months, compared to pre-discharge values.
Measured: 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
-Left ventricular reverse remodeling: ejection fraction (%) at 1, 3, and 12 months.
Measured: 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.
-Quality of life questionnare: Short-Form Health Survey (SF-36v2) with values ranging from 0 to 100 points (100 = best possible health status) at 1, 3, and 12 months.
Measured: 1, 3 and 12 months
Evaluation of the effects of losartan on functional capacity after aortic valve surgery in 1, 3 and 12 months
- 6-minute walk test (meters) at 1, 3, and 12 months.
Measured: 1, 3 and 12 months
Evaluation of the effects of losartan on kidney function after aortic valve surgery in 1, 3 and 12 months.
-Acute kidney injury (KDIGO criteria) at 1, 3, and 12 months: Stage 1: 1.5-1.9× baseline or ≥0.3 mg/dL increase Stage 2: 2.0-2.9× baseline Stage 3: 3× baseline, ≥4.0 mg/dL increase, dialysis, or clearance <35ml/min/1.73m² -Hyperkalemia (K > 5.6 mEq/L)
Measured: 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.
- Rate of cardiac rehospitalization, cardiovascular and all-cause mortality
- Rate of MACE: myocardial infarction, stroke, or cardiovascular death.
Measured: 1, 3 and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
-Left ventricular reverse remodeling: left ventricular mass index (g/m2) at 1, 3, and 12 months.
Measured: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
-Left ventricular reverse remodeling: left ventricular diameters (mm) at 1, 3, and 12 months.
Measured: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
-Left ventricular reverse remodeling: left ventricular volumes (ml) at 1, 3, and 12 months.
Measured: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
-Left ventricular reverse remodeling: left ventricular global longitudinal strain (%) at 1, 3, and 12 months.
Measured: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
-Left ventricular reverse remodeling: left ventricular myocardial work (GWI: global left ventricular myocardial work index-mmHg%) at 1, 3, and 12 months.
Measured: 1, 3, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2025
- Study start1 Jul 2025
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Heart Valve DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vitor Emer Egypto Rosa
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Sponsor-investigator, Vitor Emer Egypto Rosa, University of Sao Paulo General Hospital
- Investigators
- Vitor E. E. Rosa, MD, PhD, Principal investigator, Heart Institute of the School of Medicine of the University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07099859
- Sponsor's protocol ID
- 81900224.0.0000.0068
- Other IDs
- 2023/15710-5, 2023
- Acronym
- ARBNP
- Status last verified
- Jul 2025
- First submitted
- 8 Jul 2025
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure. Circulation. 1996 Nov 1;94(9):2285-96. doi: 10.1161/01.cir.94.9.2285.
PubMed 8901684Lang CC, Struthers AD. Targeting the renin-angiotensin-aldosterone system in heart failure. Nat Rev Cardiol. 2013 Mar;10(3):125-34. doi: 10.1038/nrcardio.2012.196. Epub 2013 Jan 15.
PubMed 23319100Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001 Dec 6;345(23):1667-75. doi: 10.1056/NEJMoa010713.
PubMed 11759645Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, Benza RL, Gottlieb SO, Kleemann TD, Rosconi F, Vandervoort PM, Cohn JN; Val-HeFT Heart Failure Trial Investigators. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002 Sep 4;40(5):970-5. doi: 10.1016/s0735-1097(02)02063-6.
PubMed 12225725Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K; Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004 Oct 26;110(17):2618-26. doi: 10.1161/01.CIR.0000146819.43235.A9. Epub 2004 Oct 18.
PubMed 15492298Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66. doi: 10.1016/s0140-6736(03)14282-1.
PubMed 13678868Della Corte A, Salerno G, Chiosi E, Iarussi D, Santarpino G, Miraglia M, Naviglio S, De Feo M. Preoperative, postoperative and 1-year follow-up N-terminal pro-B-type natriuretic peptide levels in severe chronic aortic regurgitation: correlations with echocardiographic findings. Interact Cardiovasc Thorac Surg. 2008 May;7(3):419-24; discussion 424. doi: 10.1510/icvts.2007.168039. Epub 2008 Mar 19.
PubMed 18353850Song BG, Park YH, Kang GH, Chun WJ, Oh JH, Choi JO, Lee SC, Park SW, Oh JK, Sung KI, Park P, Jeon ES. Preoperative, postoperative and one-year follow-up of N-terminal pro-B-type natriuretic peptide levels in volume overload of aortic regurgitation: comparison with pressure overload of aortic stenosis. Cardiology. 2010;116(4):286-91. doi: 10.1159/000318019. Epub 2010 Sep 22.
PubMed 20861629Rodriguez-Gabella T, Catala P, Munoz-Garcia AJ, Nombela-Franco L, Del Valle R, Gutierrez E, Regueiro A, Jimenez-Diaz VA, Ribeiro HB, Rivero F, Fernandez-Diaz JA, Pibarot P, Alonso-Briales JH, Tirado-Conte G, Moris C, Diez Del Hoyo F, Jimenez-Britez G, Zaderenko N, Alfonso F, Gomez I, Carrasco-Moraleja M, Rodes-Cabau J, San Roman Calvar JA, Amat-Santos IJ. Renin-Angiotensin System Inhibition Following Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2019 Aug 6;74(5):631-641. doi: 10.1016/j.jacc.2019.05.055.
PubMed 31370954Symeonides P, Koulouris S, Vratsista E, Triantafyllou K, Ioannidis G, Thalassinos N, Katritsis D. Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study. Eur J Echocardiogr. 2007 Dec;8(6):480-6. doi: 10.1016/j.euje.2006.09.005. Epub 2006 Nov 17.
PubMed 17113349Weber M, Arnold R, Rau M, Elsaesser A, Brandt R, Mitrovic V, Hamm C. Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease. Eur Heart J. 2005 May;26(10):1023-30. doi: 10.1093/eurheartj/ehi236. Epub 2005 Mar 21.
PubMed 15781428Tarasoutchi F, Grinberg M, Spina GS, Sampaio RO, Cardoso Lu, Rossi EG, Pomerantzeff P, Laurindo F, da Luz PL, Ramires JA. Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology. J Am Coll Cardiol. 2003 Apr 16;41(8):1316-24. doi: 10.1016/s0735-1097(03)00129-3.
PubMed 12706927Weiner RB, Baggish AL, Chen-Tournoux A, Marshall JE, Gaggin HK, Bhardwaj A, Mohammed AA, Rehman SU, Barajas L, Barajas J, Gregory SA, Moore SA, Semigran MJ, Januzzi JL Jr. Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Eur J Heart Fail. 2013 Mar;15(3):342-51. doi: 10.1093/eurjhf/hfs180. Epub 2012 Nov 6.
PubMed 23132825Daubert MA, Adams K, Yow E, Barnhart HX, Douglas PS, Rimmer S, Norris C, Cooper L, Leifer E, Desvigne-Nickens P, Anstrom K, Fiuzat M, Ezekowitz J, Mark DB, O'Connor CM, Januzzi J, Felker GM. NT-proBNP Goal Achievement Is Associated With Significant Reverse Remodeling and Improved Clinical Outcomes in HFrEF. JACC Heart Fail. 2019 Feb;7(2):158-168. doi: 10.1016/j.jchf.2018.10.014. Epub 2019 Jan 2.
PubMed 30611722Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II. Lancet. 2000 May 6;355(9215):1582-7. doi: 10.1016/s0140-6736(00)02213-3.
PubMed 10821361
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Losartan on the Neurohumoral Axis and Ventricular Remodeling of Patients With Severe Aortic Regurgitation Undergoing Valve Surgery
- ClinicalTrials.gov ID
- NCT07099859
- Acronym / sponsor ID
- ARBNP / 81900224.0.0000.0068
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Vitor Emer Egypto RosaUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- 1 Jul 2025 (actual)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 1 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Losartan group | Experimental | Drug: Losartan 50 mglosartan 50 mg/day |
| placebo group | Placebo comparator | Drug: Placeboplacebo group |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years;
- Postoperative period of aortic valve replacement surgery due to severe aortic regurgitation of any etiology;
- Signed Informed Consent Form.
Key exclusion criteria (10 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Losartan 50 mgLosartan 50 mg per day | Drug | Losartan group |
| PlaceboPlacebo 1 pill per day | Drug | placebo group |
Primary outcome
Change of NT-proBNP during the first 3 months after aortic valve surgery in patients with severe aortic regurgitation.
Time frame: 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.
11 secondary outcomes
Evaluation of the effects of losartan on NT-proBNP levels after aortic valve surgery in 1 and 12 months.
Time frame: 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
Time frame: 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.
Time frame: 1, 3 and 12 months
Evaluation of the effects of losartan on functional capacity after aortic valve surgery in 1, 3 and 12 months
Time frame: 1, 3 and 12 months
Evaluation of the effects of losartan on kidney function after aortic valve surgery in 1, 3 and 12 months.
Time frame: 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.
Time frame: 1, 3 and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
Time frame: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
Time frame: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
Time frame: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
Time frame: 1, 3, and 12 months
Evaluation of the effects of losartan on cardiac remodeling after aortic valve surgery in 1, 3 and 12 months.
Time frame: 1, 3, and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Background: PubMed 8901684Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure. Circulation. 1996 Nov 1;94(9):2285-96. doi: 10.1161/01.cir.94.9.2285.
- Background: PubMed 23319100Lang CC, Struthers AD. Targeting the renin-angiotensin-aldosterone system in heart failure. Nat Rev Cardiol. 2013 Mar;10(3):125-34. doi: 10.1038/nrcardio.2012.196. Epub 2013 Jan 15.
- Background: PubMed 11759645Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001 Dec 6;345(23):1667-75. doi: 10.1056/NEJMoa010713.
- Background: PubMed 12225725Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, Benza RL, Gottlieb SO, Kleemann TD, Rosconi F, Vandervoort PM, Cohn JN; Val-HeFT Heart Failure Trial Investigators. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002 Sep 4;40(5):970-5. doi: 10.1016/s0735-1097(02)02063-6.
- Background: PubMed 15492298Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K; Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004 Oct 26;110(17):2618-26. doi: 10.1161/01.CIR.0000146819.43235.A9. Epub 2004 Oct 18.
- Background: PubMed 13678868Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66. doi: 10.1016/s0140-6736(03)14282-1.
- Background: PubMed 18353850Della Corte A, Salerno G, Chiosi E, Iarussi D, Santarpino G, Miraglia M, Naviglio S, De Feo M. Preoperative, postoperative and 1-year follow-up N-terminal pro-B-type natriuretic peptide levels in severe chronic aortic regurgitation: correlations with echocardiographic findings. Interact Cardiovasc Thorac Surg. 2008 May;7(3):419-24; discussion 424. doi: 10.1510/icvts.2007.168039. Epub 2008 Mar 19.
- Background: PubMed 20861629Song BG, Park YH, Kang GH, Chun WJ, Oh JH, Choi JO, Lee SC, Park SW, Oh JK, Sung KI, Park P, Jeon ES. Preoperative, postoperative and one-year follow-up of N-terminal pro-B-type natriuretic peptide levels in volume overload of aortic regurgitation: comparison with pressure overload of aortic stenosis. Cardiology. 2010;116(4):286-91. doi: 10.1159/000318019. Epub 2010 Sep 22.
- Background: PubMed 31370954Rodriguez-Gabella T, Catala P, Munoz-Garcia AJ, Nombela-Franco L, Del Valle R, Gutierrez E, Regueiro A, Jimenez-Diaz VA, Ribeiro HB, Rivero F, Fernandez-Diaz JA, Pibarot P, Alonso-Briales JH, Tirado-Conte G, Moris C, Diez Del Hoyo F, Jimenez-Britez G, Zaderenko N, Alfonso F, Gomez I, Carrasco-Moraleja M, Rodes-Cabau J, San Roman Calvar JA, Amat-Santos IJ. Renin-Angiotensin System Inhibition Following Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2019 Aug 6;74(5):631-641. doi: 10.1016/j.jacc.2019.05.055.
- Background: PubMed 17113349Symeonides P, Koulouris S, Vratsista E, Triantafyllou K, Ioannidis G, Thalassinos N, Katritsis D. Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study. Eur J Echocardiogr. 2007 Dec;8(6):480-6. doi: 10.1016/j.euje.2006.09.005. Epub 2006 Nov 17.
- Background: PubMed 15781428Weber M, Arnold R, Rau M, Elsaesser A, Brandt R, Mitrovic V, Hamm C. Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease. Eur Heart J. 2005 May;26(10):1023-30. doi: 10.1093/eurheartj/ehi236. Epub 2005 Mar 21.
- Background: PubMed 12706927Tarasoutchi F, Grinberg M, Spina GS, Sampaio RO, Cardoso Lu, Rossi EG, Pomerantzeff P, Laurindo F, da Luz PL, Ramires JA. Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology. J Am Coll Cardiol. 2003 Apr 16;41(8):1316-24. doi: 10.1016/s0735-1097(03)00129-3.
- Individual participant dataSharing planned: Yes
Related trials for Heart Valve Diseases
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingObservational study
A Post-Market Assessment of the Safety and Performance of the TriClip™ System
Tricuspid Regurgitation (TR)
Active, not recruitingObservational study
Intravascular Lithotripsy in High Risk Calcified Iliac Anatomy for Transfemoral TAVR
Iliac Disease, Aortic Valve Stenosis
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vitor E. E. Rosa, MD, PhD principal investigator
Heart Institute of the School of Medicine of the University of São Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Losartan 50 mg in people with Heart Valve Diseases and Left Ventricle Remodeling, run by Vitor Emer Egypto Rosa at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vitor E. E. Rosa, MD, PhD (551126613653, vitor.rosa@hc.fm.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of NT-proBNP during the first 3 months after aortic valve surgery in patients with severe aortic regurgitation. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07099859, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2025.