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Renin-angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation (RASTAVI) (RASTAVI)

Primary Purpose

Transcatheter Aortic Valve Replacemen, Angiotensin-Converting Enzyme Inhibitors

Status

Unknown status

Phase

Phase 4

Locations

Spain

Study Type

Interventional

Intervention

Ramipril

About this trial

This is an interventional treatment trial for Transcatheter Aortic Valve Replacemen focused on measuring Cardiovascular events, Ventricular remodeling

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Transcatheter aortic valve implantation due to severe aortic stenosis.
Patients must give written informed consent.

Exclusion Criteria:

Severe mitral valvulopathy.
Reduced left ventricular ejection fraction (LVEF < 40%) with myocardial infarction or dilated cardiomyopathy.
Patients on an ACEI or an ARB the last 3 months.
History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs.
Non-MR-conditional cardiac devices.
Estimated GFR < 30 ml/min. GFR between 30 and 50 ml/min will not receive gadolinium during MRI.
Systolic blood pressure < 100 mmHg or diastolic < 40 mmHg.
Pregnant women.
Participating in other investigational trial at the time of enrollment

Sites / Locations

Hospital Clínico Universitario de Valladolid

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Ramipril

No intervention

Arm Description

After transcatheter aortic valve implantation, patients will receive ramipril before discharge plus conventional treatment (in patients without ACEI).

Conventional treatment after transcatheter aortic valve implantation

Outcomes

Primary Outcome Measures

Number of participants that had the occurrence of cardiovascular events (cardiac death, heart failure admission and stroke).

Number of participants that had first occurrence of cardiovascular events, which is defined as either cardiac death or heart failure hospitalization or stroke

Secondary Outcome Measures

Changes in left ventricular remodeling at 12 months assessed by cardiac MRI. Changes in left ventricle ejection fraction, ventricular dimenssions, ventricular mass and myocardial fibrosis will be measured

Myocardial fibrosis will be measured in grams

Change from baseline to month 12 for the six minutes walk test in order to assess functional capacity.

Assessed by six minutes walk test at 12 months

Number of patients dead due to cardiac causes.

Number of patients dead due to cardiac causes at 12 and 36 months.

Number of patients admitted due to heart failure.

Number of patients admitted due to heart failure at 12 and 36 months.

Number of patients with stroke (Defined as compatible symptoms or confirmed by imaging technique: MRI or CT) during the trial.

Number of patients with stroke during the trial at 12 and 36 months.

Number of patients - All-cause mortality

All-cause mortality measures how many patients had this event at 12 and 36 months.

Full Information

NCT ID

NCT03201185

First Posted

June 26, 2017

Last Updated

September 23, 2021

Sponsor

Hospital Clínico Universitario de Valladolid

1. Study Identification

Unique Protocol Identification Number

NCT03201185

Brief Title

Renin-angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation (RASTAVI)

Acronym

RASTAVI

Official Title

Beneficio Del Bloqueo Del Sistema Renina-angiotensina Sobre la evolución clínica y el Remodelado Ventricular Tras la colocación de Una prótesis percutánea aórtica (RASTAVI)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Unknown status

Study Start Date

February 10, 2018 (Actual)

Primary Completion Date

August 13, 2021 (Actual)

Study Completion Date

August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hospital Clínico Universitario de Valladolid

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The investigators aim to demonstrate that ramipril after transcatheter aortic valve implantation has benefits in terms of prognosis, cardiovascular events and ventricular remodeling (MRI).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Transcatheter Aortic Valve Replacemen, Angiotensin-Converting Enzyme Inhibitors

Keywords

Cardiovascular events, Ventricular remodeling

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Open-label

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

194 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ramipril

Arm Type

Experimental

Arm Description

After transcatheter aortic valve implantation, patients will receive ramipril before discharge plus conventional treatment (in patients without ACEI).

Arm Title

No intervention

Arm Type

No Intervention

Arm Description

Conventional treatment after transcatheter aortic valve implantation

Intervention Type

Drug

Intervention Name(s)

Ramipril

Intervention Description

Initial dose: 2,5 mg. Up-titrated at one month to 5 mg and 10 mg at three months (following clinical practice recommendations for up-titration). Target dose: 10 mg (or maximum tolerated dose).

Primary Outcome Measure Information:

Title

Number of participants that had the occurrence of cardiovascular events (cardiac death, heart failure admission and stroke).

Description

Number of participants that had first occurrence of cardiovascular events, which is defined as either cardiac death or heart failure hospitalization or stroke

Time Frame

Up to 36 months

Secondary Outcome Measure Information:

Title

Description

Myocardial fibrosis will be measured in grams

Time Frame

Up to 12 months

Title

Change from baseline to month 12 for the six minutes walk test in order to assess functional capacity.

Description

Assessed by six minutes walk test at 12 months

Time Frame

Up to 12 months

Title

Number of patients dead due to cardiac causes.

Description

Number of patients dead due to cardiac causes at 12 and 36 months.

Time Frame

Up to 12 and 36 months

Title

Number of patients admitted due to heart failure.

Description

Number of patients admitted due to heart failure at 12 and 36 months.

Time Frame

Up to 12 and 36 months

Title

Number of patients with stroke (Defined as compatible symptoms or confirmed by imaging technique: MRI or CT) during the trial.

Description

Number of patients with stroke during the trial at 12 and 36 months.

Time Frame

Up to 12 and 36 months

Title

Number of patients - All-cause mortality

Description

All-cause mortality measures how many patients had this event at 12 and 36 months.

Time Frame

Up to 12 and 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Transcatheter aortic valve implantation due to severe aortic stenosis. Patients must give written informed consent. Exclusion Criteria: Severe mitral valvulopathy. Reduced left ventricular ejection fraction (LVEF < 40%) with myocardial infarction or dilated cardiomyopathy. Patients on an ACEI or an ARB the last 3 months. History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs. Non-MR-conditional cardiac devices. Estimated GFR < 30 ml/min. GFR between 30 and 50 ml/min will not receive gadolinium during MRI. Systolic blood pressure < 100 mmHg or diastolic < 40 mmHg. Pregnant women. Participating in other investigational trial at the time of enrollment

Facility Information:

Facility Name

Hospital Clínico Universitario de Valladolid

City

Valladolid

ZIP/Postal Code

47005

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

8459080

Citation

Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993 Apr;21(5):1220-5. doi: 10.1016/0735-1097(93)90249-z.

Results Reference

background

PubMed Identifier

20961243

Citation

Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607. doi: 10.1056/NEJMoa1008232. Epub 2010 Sep 22.

Results Reference

background

PubMed Identifier

24678937

Citation

Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J Jr, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S, Oh JK; U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 May 8;370(19):1790-8. doi: 10.1056/NEJMoa1400590. Epub 2014 Mar 29.

Results Reference

background

PubMed Identifier

21639811

Citation

Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011 Jun 9;364(23):2187-98. doi: 10.1056/NEJMoa1103510. Epub 2011 Jun 5.

Results Reference

background

PubMed Identifier

27040324

Citation

Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, Doshi D, Cohen DJ, Pichard AD, Kapadia S, Dewey T, Babaliaros V, Szeto WY, Williams MR, Kereiakes D, Zajarias A, Greason KL, Whisenant BK, Hodson RW, Moses JW, Trento A, Brown DL, Fearon WF, Pibarot P, Hahn RT, Jaber WA, Anderson WN, Alu MC, Webb JG; PARTNER 2 Investigators. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. 2016 Apr 28;374(17):1609-20. doi: 10.1056/NEJMoa1514616. Epub 2016 Apr 2.

Results Reference

background

PubMed Identifier

28304219

Citation

Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Sondergaard L, Mumtaz M, Adams DH, Deeb GM, Maini B, Gada H, Chetcuti S, Gleason T, Heiser J, Lange R, Merhi W, Oh JK, Olsen PS, Piazza N, Williams M, Windecker S, Yakubov SJ, Grube E, Makkar R, Lee JS, Conte J, Vang E, Nguyen H, Chang Y, Mugglin AS, Serruys PW, Kappetein AP; SURTAVI Investigators. Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. 2017 Apr 6;376(14):1321-1331. doi: 10.1056/NEJMoa1700456. Epub 2017 Mar 17.

Results Reference

background

PubMed Identifier

26868689

Citation

Del Trigo M, Munoz-Garcia AJ, Wijeysundera HC, Nombela-Franco L, Cheema AN, Gutierrez E, Serra V, Kefer J, Amat-Santos IJ, Benitez LM, Mewa J, Jimenez-Quevedo P, Alnasser S, Garcia Del Blanco B, Dager A, Abdul-Jawad Altisent O, Puri R, Campelo-Parada F, Dahou A, Paradis JM, Dumont E, Pibarot P, Rodes-Cabau J. Incidence, Timing, and Predictors of Valve Hemodynamic Deterioration After Transcatheter Aortic Valve Replacement: Multicenter Registry. J Am Coll Cardiol. 2016 Feb 16;67(6):644-655. doi: 10.1016/j.jacc.2015.10.097.

Results Reference

background

PubMed Identifier

20720251

Citation

Cioffi G, Faggiano P, Vizzardi E, Tarantini L, Cramariuc D, Gerdts E, de Simone G. Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis. Heart. 2011 Feb;97(4):301-7. doi: 10.1136/hrt.2010.192997. Epub 2010 Aug 18.

Results Reference

background

PubMed Identifier

21903062

Citation

Dweck MR, Joshi S, Murigu T, Alpendurada F, Jabbour A, Melina G, Banya W, Gulati A, Roussin I, Raza S, Prasad NA, Wage R, Quarto C, Angeloni E, Refice S, Sheppard M, Cook SA, Kilner PJ, Pennell DJ, Newby DE, Mohiaddin RH, Pepper J, Prasad SK. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol. 2011 Sep 13;58(12):1271-9. doi: 10.1016/j.jacc.2011.03.064.

Results Reference

background

PubMed Identifier

8384939

Citation

Schunkert H, Jackson B, Tang SS, Schoen FJ, Smits JF, Apstein CS, Lorell BH. Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. Circulation. 1993 Apr;87(4):1328-39. doi: 10.1161/01.cir.87.4.1328.

Results Reference

background

PubMed Identifier

11300459

Citation

Fielitz J, Hein S, Mitrovic V, Pregla R, Zurbrugg HR, Warnecke C, Schaper J, Fleck E, Regitz-Zagrosek V. Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease. J Am Coll Cardiol. 2001 Apr;37(5):1443-9. doi: 10.1016/s0735-1097(01)01170-6.

Results Reference

background

PubMed Identifier

23177972

Citation

Fujisaka T, Hoshiga M, Hotchi J, Takeda Y, Jin D, Takai S, Hanafusa T, Ishizaka N. Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice. Atherosclerosis. 2013 Jan;226(1):82-7. doi: 10.1016/j.atherosclerosis.2012.10.055. Epub 2012 Nov 2.

Results Reference

background

PubMed Identifier

7743628

Citation

Litwin SE, Katz SE, Weinberg EO, Lorell BH, Aurigemma GP, Douglas PS. Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure. Circulation. 1995 May 15;91(10):2642-54. doi: 10.1161/01.cir.91.10.2642.

Results Reference

background

PubMed Identifier

1532319

Citation

Dahlof B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies. Am J Hypertens. 1992 Feb;5(2):95-110. doi: 10.1093/ajh/5.2.95.

Results Reference

background

PubMed Identifier

12034658

Citation

Diez J, Querejeta R, Lopez B, Gonzalez A, Larman M, Martinez Ubago JL. Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation. 2002 May 28;105(21):2512-7. doi: 10.1161/01.cir.0000017264.66561.3d.

Results Reference

background

PubMed Identifier

2883575

Citation

CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987 Jun 4;316(23):1429-35. doi: 10.1056/NEJM198706043162301.

Results Reference

background

PubMed Identifier

7743619

Citation

Greenberg B, Quinones MA, Koilpillai C, Limacher M, Shindler D, Benedict C, Shelton B. Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy. Circulation. 1995 May 15;91(10):2573-81. doi: 10.1161/01.cir.91.10.2573.

Results Reference

background

PubMed Identifier

24439984

Citation

Dalsgaard M, Iversen K, Kjaergaard J, Grande P, Goetze JP, Clemmensen P, Hassager C. Short-term hemodynamic effect of angiotensin-converting enzyme inhibition in patients with severe aortic stenosis: a placebo-controlled, randomized study. Am Heart J. 2014 Feb;167(2):226-34. doi: 10.1016/j.ahj.2013.11.002. Epub 2013 Nov 9.

Results Reference

background

PubMed Identifier

25796267

Citation

Bull S, Loudon M, Francis JM, Joseph J, Gerry S, Karamitsos TD, Prendergast BD, Banning AP, Neubauer S, Myerson SG. A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis (RIAS trial). Eur Heart J Cardiovasc Imaging. 2015 Aug;16(8):834-41. doi: 10.1093/ehjci/jev043. Epub 2015 Mar 21.

Results Reference

background

PubMed Identifier

25012498

Citation

Bang CN, Greve AM, Kober L, Rossebo AB, Ray S, Boman K, Nienaber CA, Devereux RB, Wachtell K. Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis. Int J Cardiol. 2014 Aug 20;175(3):492-8. doi: 10.1016/j.ijcard.2014.06.013. Epub 2014 Jun 28.

Results Reference

background

PubMed Identifier

21798417

Citation

Nadir MA, Wei L, Elder DH, Libianto R, Lim TK, Pauriah M, Pringle SD, Doney AD, Choy AM, Struthers AD, Lang CC. Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis. J Am Coll Cardiol. 2011 Aug 2;58(6):570-6. doi: 10.1016/j.jacc.2011.01.063.

Results Reference

background

PubMed Identifier

15222281

Citation

Lund O, Erlandsen M, Dorup I, Emmertsen K, Flo C, Jensen FT. Predictable changes in left ventricular mass and function during ten years after valve replacement for aortic stenosis. J Heart Valve Dis. 2004 May;13(3):357-68.

Results Reference

background

PubMed Identifier

15821660

Citation

Gjertsson P, Caidahl K, Farasati M, Oden A, Bech-Hanssen O. Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients with severe aortic stenosis. J Thorac Cardiovasc Surg. 2005 Apr;129(4):890-6. doi: 10.1016/j.jtcvs.2004.09.004.

Results Reference

background

PubMed Identifier

25449483

Citation

Yiu KH, Ng WS, Chan D, Sit KY, Wong A, Lee CW, Chum HL, Cheng WY, Pun CT, Ho KL, Chen Y, Ho LM, Kumana CR, Cheung HL, Chung MC, Lau CP, Au WK, Tse HF. Improved prognosis following renin-angiotensin-aldosterone system blockade in patients undergoing concomitant aortic and mitral valve replacement. Int J Cardiol. 2014 Dec 15;177(2):680-2. doi: 10.1016/j.ijcard.2014.09.163. Epub 2014 Oct 5. No abstract available.

Results Reference

background

PubMed Identifier

25402513

Citation

Goel SS, Aksoy O, Gupta S, Houghtaling PL, Tuzcu EM, Marwick T, Mihaljevic T, Svensson L, Blackstone EH, Griffin BP, Stewart WJ, Barzilai B, Menon V, Kapadia SR. Renin-angiotensin system blockade therapy after surgical aortic valve replacement for severe aortic stenosis: a cohort study. Ann Intern Med. 2014 Nov 18;161(10):699-710. doi: 10.7326/M13-1505.

Results Reference

background

PubMed Identifier

20723651

Citation

Dahl JS, Videbaek L, Poulsen MK, Pellikka PA, Veien K, Andersen LI, Haghfelt T, Moller JE. Effect of candesartan treatment on left ventricular remodeling after aortic valve replacement for aortic stenosis. Am J Cardiol. 2010 Sep 1;106(5):713-9. doi: 10.1016/j.amjcard.2010.04.028. Epub 2010 Jul 23.

Results Reference

background

PubMed Identifier

10639539

Citation

Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301. Erratum In: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748.

Results Reference

background

PubMed Identifier

32470515

Citation

Amat-Santos IJ, Santos-Martinez S, Lopez-Otero D, Nombela-Franco L, Gutierrez-Ibanes E, Del Valle R, Munoz-Garcia E, Jimenez-Diaz VA, Regueiro A, Gonzalez-Ferreiro R, Benito T, Sanmartin-Pena XC, Catala P, Rodriguez-Gabella T, Delgado-Arana JR, Carrasco-Moraleja M, Ibanez B, San Roman JA. Ramipril in High-Risk Patients With COVID-19. J Am Coll Cardiol. 2020 Jul 21;76(3):268-276. doi: 10.1016/j.jacc.2020.05.040. Epub 2020 May 26.

Results Reference

derived

PubMed Identifier

31370954

Citation

Rodriguez-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.

Results Reference

derived

PubMed Identifier

29440218

Citation

Amat-Santos IJ, Catala P, Diez Del Hoyo F, Fernandez-Diaz JA, Alonso-Briales JH, Del Trigo M, Regueiro A, Juan-Salvadores P, Serra V, Gutierrez-Ibanes E, Munoz-Garcia AJ, Nombela-Franco L, Sabate M, Jimenez-Diaz VA, Garcia Del Blanco B, Lopez J, Varela-Falcon LH, Sevilla T, Arnold R, Revilla A, San Roman JA. Impact of renin-angiotensin system inhibitors on clinical outcomes and ventricular remodelling after transcatheter aortic valve implantation: rationale and design of the RASTAVI randomised multicentre study. BMJ Open. 2018 Feb 13;8(2):e020255. doi: 10.1136/bmjopen-2017-020255.

Results Reference

derived

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Renin-angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation (RASTAVI)

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