Losartan for Coarctation of the Aorta (VALUE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Mayo Clinic
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the effectiveness and mechanism of action of Losartan in the treatment of coarctation of aorta.
Will I have to stop taking my current medications?
If you are currently taking beta blockers or have received any antihypertensive medications in the past year, you cannot participate in this trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.
Is losartan safe for humans?
Losartan is generally well tolerated in humans, with a low chance of causing kidney problems, but there have been rare cases of severe skin reactions linked to its use.
12345How does the drug Losartan differ from other treatments for coarctation of the aorta?
Losartan is unique because it targets the renin-angiotensin system, which is involved in blood pressure regulation, and may help manage hypertension (high blood pressure) associated with coarctation of the aorta. Unlike surgical options that directly address the physical narrowing of the aorta, Losartan offers a non-surgical approach by potentially reducing blood pressure through its action on angiotensin receptors.
678910Eligibility Criteria
This trial is for adults with a history of early childhood repair of coarctation of the aorta and slightly elevated blood pressure. They must not be on beta blockers, pregnant, or have severe kidney issues, high potassium levels, significant heart valve problems, coronary artery disease, or taken blood pressure meds in the last year.Inclusion Criteria
My average blood pressure is between 120-139.
Exclusion Criteria
I have taken medication for high blood pressure in the last year.
I am currently taking beta blocker medication.
I have severe heart valve issues.
I have been diagnosed with coronary artery disease.
Participant Groups
The study is testing Losartan's effectiveness against cardiovascular remodeling in patients who've had an aortic coarctation repair. It compares Losartan to Amlodipine and placebo to see which better improves heart structure and function.
3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Losartan GroupExperimental Treatment1 Intervention
Subjects with Coarctation of Aorta (COA) and high blood pressure will receive Losartan.
Group II: Amlodipine GroupActive Control1 Intervention
Subjects with Coarctation of Aorta (COA) and high blood pressure will receive Amlodipine.
Group III: Placebo GroupPlacebo Group1 Intervention
Subjects with Coarctation of Aorta (COA) and high blood pressure will receive Placebo.
Losartan is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Cozaar for:
- Hypertension
- Diabetic nephropathy
- Stroke prevention in hypertension and left ventricular hypertrophy
🇪🇺 Approved in European Union as Cozaar for:
- Hypertension
- Diabetic nephropathy
- Heart failure
🇨🇦 Approved in Canada as Cozaar for:
- Hypertension
- Diabetic nephropathy
- Heart failure
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
Loading ...
Who is running the clinical trial?
Mayo ClinicLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Comparative antihypertensive effects of losartan 50 mg and losartan 50 mg titrated to 100 mg in patients with essential hypertension. [2019]The antihypertensive activity of losartan potassium (losartan, Cozaar), an angiotensin II receptor antagonist, was evaluated in a parallel 12-week, double-blind, placebo-controlled trial in hypertensive patients with mild-to-moderate hypertension. After a 4-week, single-blind, placebo lead-in period, which included monitoring of baseline variables, 366 patients with a group mean sitting diastolic blood pressure of 101 +/- 5 (s.d.) mmHg were assigned randomly to one of three treatment groups: placebo, losartan 50 mg, or losartan 50 mg with the option to titrate to 100 mg after the first 6 weeks if the target sitting diastolic blood pressure ( or = 90 mmHg at week 6 were mock titrated (changed to a new tablet containing the same study medication and dose). Sitting diastolic blood pressure was also evaluated at the end of the trial during a 1-week off-drug period to assess for rebound hypertension. At week 6, patients in the active-drug-treatment arms experienced significantly greater peak (6 h post-dose) and trough (24 h post-dose) reduction in systolic and diastolic sitting blood pressures compared with placebo (p
Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome. [2016]It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates losartan effectiveness in genetically classified subgroups.
Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial. [2017]To determine the efficacy of losartan vs. atenolol in aortic dilation progression in Marfan syndrome (MFS) patients.
Losartan in heart failure: preclinical experiences and initial clinical outcomes. [2019]Losartan potassium (Cozaar) is an angiotensin II receptor antagonist (AT1 selective) which has undergone extensive clinical trials for the treatment of hypertension. This literature survey will review some of the pre-clinical findings with losartan in models of heart failure, and where appropriate, we will compare the haemodynamic findings in animals with similar studies completed in patients. The major conclusion from these trials is that losartan has clear haemodynamic benefits in patients in heart failure and that the drug appears to be well tolerated, with a low incidence of adverse experiences related to impaired renal function.
[Severe pustular and polymorphous vasculitis caused by losartan]. [2022]We report a case of severe pustular vasculitis most probably due to losartan (Cozaar) which is an antihypertensive drug inhibiting the receptors for angiotensin II.
Studies of plasma renin activity in coarctation of the aorta. [2019]Experimental and clinical studies were performed to assess the role of the renin-angiotensin system in producing hypertension in coarctation of the aorta. Basal and stimulated peripheral plasma renin activity were determined in the canine model and in four patients with coarctation. The animal studies showed no significant elevation of peripheral plasma renin activity (PPRA), and no increase in the response of PPRA to stimuli. The human studies showed a significant elevation in the response to PPRA to postural change and to exercise in three of four patients with coarctation, as compared to the same patients after correction of the coarctation. It is concluded that hyperactivity of the renin-angiotensin system is not the primary cause in coarctation hypertension in dog or man. It is nonetheless probable that the renin-angiotensin system has a role in coarctation hypertension, and further studies will be necessary to determine its place.
Activation of upregulated angiotensin II type 2 receptors decreases carotid pulse pressure in rats with suprarenal abdominal aortic coarctation. [2018]Our aim was to determine whether angiotensin type 2 receptors (AT2R) are involved in the depression of carotid pulse pressure (PP) in rats with suprarenal aortic coarctation (SrC). We tested the effects of losartan, PD123319, and CGP42112 on PP in SrC and Sham-operated anesthetized rats. PP increased in SrC rats. Neither losartan nor PD123319 affected PP in SrC and Sham-operated rats. CGP42112 reduced PP, in SrC rats, combined with losartan. Moreover, PD123319 blocked this effect. AT2R protein increased in the thoracic aortas of SrC rats. Thus, upregulated AT2R stimulation by CGP42112 mediates depression of PP in rats under pressure overloading.
Preoperative and postoperative renin levels in coarctation of the aorta. [2019]We studied plasma renin activity (PRA) in eight children before and after surgical correction of aortic coarctation. These eight children underwent a combination of low-sodium diet and diuresis before surgery, and PRA was measured shortly thereafter. Thirty-two to 51 months after successful surgical correction, PRA was measured again. The mean PRA was 21.4 +/- 1.3 ng/ml/hour (+/- SD) preoperatively and 5.5 +/- 1.5 ng/ml/hour postoperatively. These findings provide further evidence of the significance of increased renin-angiotensin activity in patients with aortic coarctation.
Coarctation of the abdominal aorta: current options in surgical management. [2022]Coarctation or hypoplasia of the abdominal aorta is a rare cause of life-threatening hypertension. In most cases the mechanism of hypertension is elevated blood renin levels secondary to associated renal artery stenosis. Medical control of the hypertension is often difficult, and thus patients usually require renal artery revascularization combined with aortic bypass or replacement early in life. Current surgical management should optimize the use of autogenous methods of renal artery reconstruction including saphenous vein aortorenal bypass, splenorenal arterial anastomosis, hepatorenal saphenous vein bypass, and renal autotransplantation. In selected patients the reconstruction can be staged by correction of the renal artery stenosis and postponement of definitive repair of the aortic coarctation until it becomes hemodynamically significant.
[Role of the renin-angiotensin system in arterial hypertension with aortic coarctation in young adults]. [2009]The renin-angiotensin system (RAS) was evaluated in 7 hypertensives with pure isthmic coarctation of the aorta. RAS was studied under basal conditions, standing, after saralasine (a specific angiotensin II antagonist) and after acebutolol (a cardioselective beta-blocker and an inhibitor of renin secretion). Plasma volume was measured by radio isotopic methods and cardiac catheterisation was performed to assess the pressure gradient across the coarctation. On a normal salt diet on orthostatism, plasma renin activity (PRA) was increased in 5 patients and normal in the other 2. After moderate salt depletion, saralasine injection caused a significant fall in diastolic blood pressure (89,2 +/- 4,4 to 77,3 +/- 6,6 mmHg; p