Reactive Oxygen Species Following Aortic Valve Replacement

NCT02841917 | Completed

• 1 other identifier: RHM CAR0508
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Surgical aortic valve replacement (SVAR) is currently the 'Gold Standard' therapy for patients with severe symptomatic aortic stenosis (AS). Approximately 30-50% of patients with severe AS are deemed inoperable due to comorbidities such as severe respiratory disease, chronic renal disease and peripheral vascular disease. Transcatheter aortic valve replacement (TAVR) has emerged as a novel therapeutic modality for inoperable patients and an effective alternative to SAVR in selected high and intermediate-risk patients. Myocardial ischemia and reperfusion injury (MRI), mediated by reactive oxygen species (ROS), related to cardiopulmonary bypass has been linked to adverse clinical outcomes following cardiac surgery. In contrast to SAVR, transcatheter deployment of aortic prostheses requires shorter time of ischemia and hypotension and may be associated with less ROS mediated MRI. Inflammatory responses and reperfusion injury following TAVR have not been previously described nor compared to SAVR. The aim of this study is therefore to compare the oxidative stress response in patients with isolated severe symptomatic AS undergoing SAVR or TAVR and determine whether it correlates with clinical outcomes.

Conditions

Aortic Stenosis

Outcome Measures

Primary Outcomes (1)

• Ascertain the concentrations of serum isoprostanes, nitrites and sulphides following transcatheter and surgical aortic valve replacement.

  Serum measurements will be undertaken using standard immunoassay techniques.

  24 hours

Secondary Outcomes (4)

• Ascertain potential differences in the generation of reactive oxygen species that have been outlined in the primary outcomes with cardiovascular mortality.

  30 days clinical follow-up

• Ascertain potential differences in the generation of reactive oxygen species that have been outlined in the primary outcomes with myocardial infarction.

  30 days clinical follow-up.

• Ascertain potential differences in the generation of reactive oxygen species that have been outlined in the primary outcomes with stroke.

  30 days clinical follow-up.

• Ascertain potential differences in the generation of reactive oxygen species that have been outlined in the primary outcomes with major bleeding.

  30 days clinical follow-up.

Study Arms (2)

Transcatheter Aortic Valve Replacement

ROS Post TAVR

Surgical Aortic Valve Replacement

ROS Post SAVR

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with severe symptomatic aortic stenosis undergoing transcatheter or surgical aortic valve replacement.

You may qualify if:

• \. Severe symptomatic aortic stenosis defined as aortic valve area \<1 cm2, mean aortic gradient \>40 mm Hg or Vmax \> 4 m/s amenable for transcatheter or surgical aortic valve replacement.

You may not qualify if:

• Severe comorbidities , advance age, frailty or thoracic anatomy unfavorable for surgical aortic valve replacement.
• Anatomy precluding transcatheter aortic valve replacement.
• Requirement for concomitant coronary artery bypass grafting.
• Requirement for concomitant mitral, tricuspid, or pulmonary valve surgery.
• Allergy to aspirin or clopidogrel.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead

Study Sites (1)

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Related Publications (12)

• Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Creager MA, Curtis LH, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Stevenson WG, Yancy CW; American College of Cardiology; American College of Cardiology/American Heart Association; American Heart Association. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg. 2014 Jul;148(1):e1-e132. doi: 10.1016/j.jtcvs.2014.05.014. Epub 2014 May 9. No abstract available.

  PMID: 24939033 RESULT

• Bach DS, Siao D, Girard SE, Duvernoy C, McCallister BD Jr, Gualano SK. Evaluation of patients with severe symptomatic aortic stenosis who do not undergo aortic valve replacement: the potential role of subjectively overestimated operative risk. Circ Cardiovasc Qual Outcomes. 2009 Nov;2(6):533-9. doi: 10.1161/CIRCOUTCOMES.109.848259. Epub 2009 Oct 27.

  PMID: 20031890 RESULT

• 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.

  PMID: 20961243 RESULT

• 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.

  PMID: 21639811 RESULT

• Larmann J, Theilmeier G. Inflammatory response to cardiac surgery: cardiopulmonary bypass versus non-cardiopulmonary bypass surgery. Best Pract Res Clin Anaesthesiol. 2004 Sep;18(3):425-38. doi: 10.1016/j.bpa.2003.12.004.

  PMID: 15212337 RESULT

• Scolletta S, Carlucci F, Biagioli B, Marchetti L, Maccherini M, Carlucci G, Rosi F, Salvi M, Tabucchi A. NT-proBNP changes, oxidative stress, and energy status of hypertrophic myocardium following ischemia/reperfusion injury. Biomed Pharmacother. 2007 Feb-Apr;61(2-3):160-6. doi: 10.1016/j.biopha.2006.10.007. Epub 2007 Feb 20.

  PMID: 17350221 RESULT

• Cavalca V, Tremoli E, Porro B, Veglia F, Myasoedova V, Squellerio I, Manzone D, Zanobini M, Trezzi M, Di Minno MN, Werba JP, Tedesco C, Alamanni F, Parolari A. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: patterns and differences. Interact Cardiovasc Thorac Surg. 2013 Dec;17(6):923-30. doi: 10.1093/icvts/ivt386. Epub 2013 Sep 7.

  PMID: 24014619 RESULT

• Hausenloy DJ, Yellon DM. The evolving story of "conditioning" to protect against acute myocardial ischaemia-reperfusion injury. Heart. 2007 Jun;93(6):649-51. doi: 10.1136/hrt.2007.118828.

  PMID: 17502643 RESULT

• Rodrigo R, Korantzopoulos P, Cereceda M, Asenjo R, Zamorano J, Villalabeitia E, Baeza C, Aguayo R, Castillo R, Carrasco R, Gormaz JG. A randomized controlled trial to prevent post-operative atrial fibrillation by antioxidant reinforcement. J Am Coll Cardiol. 2013 Oct 15;62(16):1457-65. doi: 10.1016/j.jacc.2013.07.014. Epub 2013 Jul 31.

  PMID: 23916928 RESULT

• Granger DN. Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol. 1988 Dec;255(6 Pt 2):H1269-75. doi: 10.1152/ajpheart.1988.255.6.H1269.

  PMID: 3059826 RESULT

• Zimmerman JJ. Defining the role of oxyradicals in the pathogenesis of sepsis. Crit Care Med. 1995 Apr;23(4):616-7. doi: 10.1097/00003246-199504000-00003. No abstract available.

  PMID: 7712748 RESULT

• Macdonald J, Galley HF, Webster NR. Oxidative stress and gene expression in sepsis. Br J Anaesth. 2003 Feb;90(2):221-32. doi: 10.1093/bja/aeg034.

  PMID: 12538380 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be taken for measurement of reactive oxygen species

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Michael Mahmoudi, MD,PhD

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Gabriel Maluenda, MD

  Centro Cardiovascular, Hospital San Borja, Chile

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 22, 2016
• Study Start: November 29, 2016
• Primary Completion: March 31, 2017
• Study Completion: March 31, 2017
• Last Updated: September 6, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)