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Trial record 70 of 228 for:    Recruiting, Not yet recruiting, Available Studies | Aortic stenosis

Efficacy of Angiotensin Receptor Blocker Following aortIc Valve Intervention for Aortic STenOsis: a Randomized mulTi-cEntric Double-blind Phase II Study (ARISTOTE)

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ClinicalTrials.gov Identifier: NCT03315832
Recruitment Status : Not yet recruiting
First Posted : October 20, 2017
Last Update Posted : January 28, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges

Brief Summary:

Aortic stenosis (AS) is the most frequent valvular heart disease in Western countries, with increasing prevalence. Recent guidelines recommend aortic valve intervention (surgical aortic valve replacement [SAVR] or transcatheter aortic valve replacement [TAVR]) in severe AS, as soon as symptoms or left ventricular (LV) dysfunction occur, in order to improve clinical outcome and achieve LV mass (LVM) regression. The highest amount of LVM regression is obtained during the first year. Nevertheless, there is heterogeneity in LV remodeling and residual LV hypertrophy is associated with poorer postoperative improvement in cardiac function and morphology. Incomplete regression of LV hypertrophy at 12 months after SAVR is a powerful predictor of adverse outcome. Yet, the use of specific pharmacological therapy to improve postoperative LVM regression could be an appealing therapeutic option after aortic valve intervention.

Renin-angiotensin-aldosterone system blockers (RAASb) and more particularly angiotensin-II receptor blockers (ARBs) are efficient in reducing LVM in hypertensive patients, as emphasized by several meta-analyses. In addition, ARBs improve myocardial relaxation, diastolic function, decreased hypertrophy and may have anti-fibrotic effects. In a recent retrospective study from our group, RAASb prescription after SAVR was associated with increased survival, but confirmation through a randomized trial is mandatory. In a prospective randomized single-center study, the use of candesartan was associated both with LV and LA remodeling as compared to the conventional management. Nevertheless, these results are based on echocardiographic data, which is not the gold standard for the assessment cardiac remodeling, and no placebo or active comparator was tested to control the impact of ARBs in these patients.

The primary objective of this Phase II study is to investigate the efficacy of valsartan, introduced postoperatively, as compared to placebo, on 1-year changes in indexed LVM, as assessed by CMR, in patients undergoing aortic valve intervention (SAVR or TAVR) for AS.

The secondary objectives are to compare the efficacy of valsartan vs. placebo in terms of one-year changes (difference from baseline) in cardiac function and in cardiac morphology, one-year exercise capacity and one-year changes in biomarkers related to cardiac function. In addition, the assessment of the safety of valsartan will also be considered as secondary objective.

The ARISTOTE trial is a multicenter prospective phase II, randomized, double-blind study including patients with the diagnosis of severe AS and indication for valve intervention.

The active treatment is valsartan, an orally active, potent, and specific angiotensin II receptor antagonist.

Patients will be randomized between 2 groups (valsartan versus placebo) and the treatment will be initiated (80 mg daily) at 5±4 days following aortic valve intervention. The comparative treatment will be a placebo; tablets of valsartan and placebo have a similar appearance and administration mode. Patient in the control group will receive a placebo using the same protocol as the valsartan group.

The patients will be cautiously monitored and any adverse events will be collected. The dose will be increased at 160 mg daily 13±2 days after aortic valve intervention and, if well tolerated, for the remaining period of the study. The tolerance will be regularly assessed and dose adjusted according to a pre-specified algorithm.


Condition or disease Intervention/treatment Phase
Aortic Valve Stenosis Valsartan Angiotensin Receptor Antagonists Transcatheter Aortic Valve Replacement Heart Valve Prosthesis Implantation Hypertrophy, Left Ventricular Drug: Valsartan Drug: Placebo Oral Tablet Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients with the diagnosis of severe AS and indication for valve intervention (i.e. SAVR or TAVR) fulfilling all inclusion/exclusion criteria will be randomized using 1:1 ratio.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Angiotensin Receptor Blocker Following aortIc Valve Intervention for Aortic STenOsis: a Randomized mulTi-cEntric Double-blind Phase II Study
Estimated Study Start Date : October 2, 2019
Estimated Primary Completion Date : April 2, 2022
Estimated Study Completion Date : May 2, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Valsartan

Arm Intervention/treatment
Experimental: Valsartan
The active treatment is valsartan, an orally active, potent, and specific angiotensin II receptor antagonist. The treatment will be initiated (80 mg, daily) at 5±4 days following aortic valve intervention. The dose will be increased at 160 mg daily 13±2 days after aortic valve intervention and, if well tolerated, for the remaining period of the study.
Drug: Valsartan
The active treatment is valsartan, an orally active, potent, and specific angiotensin II receptor antagonist. The treatment will be initiated (80 mg, daily) at 5±4 days following aortic valve intervention. The dose will be increased at 160 mg daily 13±2 days after aortic valve intervention and, if well tolerated, for the remaining period of the study.

Placebo Comparator: Placebo Oral Tablet
The comparative treatment will be a placebo; tablets of valsartan and placebo have a similar appearance and administration mode. Patient in the control group will receive a placebo using the same protocol as the valsartan group.
Drug: Placebo Oral Tablet
The comparative treatment will be a placebo; tablets of valsartan and placebo have a similar appearance and administration mode. Patient in the control group will receive a placebo using the same protocol as the valsartan group.




Primary Outcome Measures :
  1. Indexed left ventricular mass [ Time Frame: Day 0 to Year 1 ]
    the 1-year change from baseline in indexed LVM after aortic valve intervention as assessed using cardiac magnetic resonance (CMR)


Secondary Outcome Measures :
  1. Left ventricular global longitudinal strain [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in left ventricular global longitudinal strain quantified using CMR

  2. Left ventricular global longitudinal strain [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Left ventricular global longitudinal strain quantified using transthoracic echocardiography (TTE)

  3. Left atrial volume [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Left atrial volume quantified using CMR

  4. Left atrial volume [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Left atrial volume quantified using TTE

  5. Indexed left ventricular mass [ Time Frame: Day 0 to Year 1 ]
    the 1-year change from baseline in indexed LVM after aortic valve intervention as assessed using TTE (real-time 3D)

  6. Native T1 [ Time Frame: Day 0 to Year 1 ]
    the 1-year change from baseline in native T1 using CMR

  7. Rate of late gadolinium enhancement (LGE) [ Time Frame: Day 0 to Year 1 ]
    the 1-year change from baseline in rate of LGE using CMR

  8. Volume of late gadolinium enhancement (LGE) [ Time Frame: Day 0 to Year 1 ]
    the 1-year change from baseline in volume of LGE using CMR

  9. Extra cellular volume [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in extra cellular volume using CMR

  10. Indexed interstitial volume [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Indexed interstitial volume using CMR

  11. Electrocardiographic strain [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Electrocardiographic strain

  12. Left ventricular ejection fraction [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Left ventricular ejection fraction using CMR

  13. Left ventricular ejection fraction [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in Left ventricular ejection fraction using TTE

  14. Peak exercise VO2 [ Time Frame: Year 1 ]
    The 1-year measurement of Peak exercise VO2

  15. VE/VCO2 ratio [ Time Frame: 1 year ]
    The 1-year measurement of VE/VCO2 ratio

  16. Maximal load [ Time Frame: 1 year ]
    The 1-year maximal load reached

  17. New-York heart association functional class [ Time Frame: 1 year ]
    The 1-year assessment of New-York heart association functional class

  18. Exercise oscillatory ventilation rate [ Time Frame: 1 year ]
    The 1-year quantification of exercise oscillatory ventilation rate

  19. Nt-pro Brain natriuretic peptide [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in level of Nt-pro Brain natriuretic peptide using immunoassay

  20. Plasma cardiac troponin I [ Time Frame: Day 0 to Year 1 ]
    The 1-year change from baseline in concentration of Plasma cardiac troponin I using high-sensitivity assay

  21. Incidence of treatment-Emergent Adverse Events [ Time Frame: Day 1 to Month 13 ]
    Clinical occurrence of adverse events (AEs) and serious adverse events (SAEs) during the duration of the study period ending month 13



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men with age ≥18 years
  • Women at postmenopausal state as defined by absence of menses for the last 12 months without alternative medical cause.
  • Severe AS, defined according most recent guidelines (aortic valve area <1.0cm² or <0.6cm²/m² and aortic mean pressure gradient ≥40mmHg or aortic maximal velocity >4m/s, as assessed using transthoracic echocardiography [TTE]).
  • Indication for aortic valve intervention
  • Affiliation to the French Social Security system
  • Signed informed consent.

Exclusion Criteria:

  • Patients already under any Renin-Angiotensin-Aldosterone System blockers (RAASb) prior to randomization.
  • Concomitant coronary artery bypass graft or other valvular intervention
  • Other significant left-sided valvular heart diseases (≥moderate), even without concomitant procedure
  • Any contra-indication to CMR
  • Chronic kidney disease with estimated glomerular filtration rate (GFR) <30 ml/min
  • Prior or planned organ transplantation
  • Hyperkaliemia (kaliemia >5.5 mmol/L at inclusion visit)
  • Severe hepatic failure, biliary cirrhosis, cholestasis
  • Combined use of aliskiren and concomitant diabetes mellitus or renal failure with GFR<60mL/min/1.73m²
  • Low systolic blood pressure (<100mmHg)
  • History of angioedema
  • History of hypersensitivity or allergy to Angiotensin-II Receptor Blockers or excipient
  • Under legal authority.
  • Unwilling to consent

Secondary Exclusion Criteria:

  • Patients not under RAASb prior to randomization but who should benefit from this treatment to improve outcome:
  • Heart failure with reduced ejection fraction (<40%)
  • Coronary artery disease
  • Clinical peripheral artery disease
  • History of cerebrovascular disease
  • Uncontrolled hypertension despite the use of other therapeutic classes
  • Diabetes mellitus
  • Impossibility to perform randomization into the 9-day post-intervention period due to per procedural complication with prolonged stay in intensive cardiac care unit (including death).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03315832


Contacts
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Contact: Victor ABOYANS, MD 555058953 ext +33 victor.aboyans@chu-limoges.fr
Contact: Julien MAGNE, PhD 555056310 ext +33 julien.magne@chu-limoges.fr

Locations
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France
Limoges university hospital Not yet recruiting
Limoges, France, 87042
Contact: Victor ABOYANS, MD    555058953 ext +33    victor.aboyans@chu-limoges.fr   
Contact: Julien MAGNE, PhD    555056310 ext +33    julien.magne@chu-limoges.fr   
Principal Investigator: Victor ABOYANS, MD         
Sponsors and Collaborators
University Hospital, Limoges

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Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT03315832     History of Changes
Other Study ID Numbers: I16007 (ARISTOTE)
First Posted: October 20, 2017    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Limoges:
Aortic Valve Stenosis
Valsartan
Angiotensin Receptor Antagonists
Transcatheter Aortic Valve Replacement
Heart Valve Prosthesis Implantation
double-blind phase II study
left ventricular mass

Additional relevant MeSH terms:
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Constriction, Pathologic
Aortic Valve Stenosis
Hypertrophy
Hypertrophy, Left Ventricular
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Cardiomegaly
Valsartan
Angiotensin Receptor Antagonists
Angiotensin II
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents