Parasternal vs. Sternotomy Approach for Conventional Aortic Valve Replacement (PASTA)

• ClinicalTrials.gov Identifier: NCT04632095
• Recruitment Status: Recruiting
• First Posted: November 17, 2020
• Last Update Posted: March 23, 2021
• Sponsor: Jena University Hospital
• Collaborator: The German Heart Foundation
• Information provided by (Responsible Party): Jena University Hospital

Study Description

Brief Summary:

Prospective randomized study comparing aortic valve replacement using parasternal or sternotomy access with regard to quality of life and systemic inflammatory reaction.

Condition or disease	Intervention/treatment	Phase
Aortic Valve Stenosis	Procedure: Aortic valve replacement due to sternotomy; Procedure: Aortic valve replacement due to parasternal right anterior mini-thoracotomy	Not Applicable

Detailed Description:

The classic surgical treatment of aortic stenosis is valve replacement through complete midline opening of the breastbone (median sternotomy) and use of cardiopulmonary bypass (CPB). Risks of this procedure are related to both the surgical approach and the use of CPB. Using minimally invasive approaches in non-cardiac patients (e.g laparoscopy) resulted in reduced postoperative inflammatory response when compared to patients undergoing the same procedures carried out with a conventional "open" technique. Minimally invasive surgical approaches in which the sternum is partially opened (partial sternotomy) or not opened at all (parasternal access) have thus far shown similar procedure related mortality and lower incidence of perioperative complications, despite longer CPB times. Our single center experience thus far suggests superiority of parasternal aortic valve replacement (O/E ratio of 0.19 over the last 2 years), as well as a reduced postoperative inflammatory response (as measured by lower CRP (C reactive protein ) levels taken 6 hours post-surgery). However, these data have several confounders and there is currently no prospective randomized trial addressing this topic. We therefore conduct a randomized comparison of parasternal versus classic sternotomy aortic valve replacement. Based on our previous experience, we expect very low mortality risk in both groups (expected ≤ 1%). The primary endpoint is therefore quality of life assessed using the SF-36 (Short Form) health survey questionnaire. This approach is similar to other current large multicenter trials. In order to address the impact of reduced surgical trauma on inflammatory response; we will quantify an established panel of inflammatory markers (PCT, CRP, interleukin 6) and use bio-banking to allow for further in depth analysis later on. Standardized clinical endpoints will be analyzed as additional secondary parameters. Power analysis determined a number of 50 patients allocated to 2 equal groups to achieve a power of 80%. The parasternal approach is expected to be superior when compared to sternotomy in both the primary and some, if not most, secondary endpoints. We expect our study to become an important milestone for decision-making in the treatment of aortic stenosis. Patients currently fear sternotomy, but the less invasive transcatheter valve implantation appears to be limited by inferior long-term outcome. The parasternal, sternotomy-sparing, classic aortic valve replacement is therefore an attractive therapeutic alternative. Our investigation in relation to systemic inflammatory response will further shed light on the underlying mechanisms explaining differences in clinical outcomes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Parasternal vs. Sternotomy Approach for Conventional Aortic Valve Replacement
• Actual Study Start Date: March 16, 2021
• Estimated Primary Completion Date: March 16, 2022
• Estimated Study Completion Date: November 15, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sternotomy AVR; Aortic valve replacement due to sternotomy	Procedure: Aortic valve replacement due to sternotomy; conventional surgery of aortic stenosis
Active Comparator: Mini AVR; Aortic valve replacement due to parasternal right anterior mini-thoracotomy	Procedure: Aortic valve replacement due to parasternal right anterior mini-thoracotomy; surgery of aortic stenosis in minimally invasive technique

Outcome Measures

Primary Outcome Measures :

1. Quality of life - physical function [ Time Frame: 30 days after surgery ]
   Comparison of the physical quality of life between the two groups 30 days after surgery using the physical function score of the 36-Item Short Form Health Survey (SF-36). The physical function score is a scale from 0 (poor physical function) to 100 (excellent physical function, with an average score of 50. It includes items that assess physical functioning, bodily pain, physical role functioning, vitality, and generaly health perceptions.

Secondary Outcome Measures :

1. Inflammatory markers: Procalcitonin, C-reactive protein, Interleukin-6 [ Time Frame: During the first 48 hours after surgery ]
   Plasma profiles of inflammatory biomarkers at defined time points in the course of the surgical intervention (baseline, before introduction of CPB, 1 hour after introduction of CPB, disconnection of CPB, 6, 24 and 48 hours post-surgery)
2. Quality of Life - mental function [ Time Frame: 30 days after surgery ]
   Comparison of the mental quality of life between the two Groups 30 days after surgery using the mental component score of the 36-Item Short Form Health Survey (SF-36). The mental function score is a scale from 0 (poor mental quality of life) to 100 (excellent mental quality of life), with an average score of 50. It includes items that assess vitality, general health perceptions, emotional role functioning, social role functioning, and mental health.
3. Duration of the Operation [ Time Frame: During the aortic valve replacement surgery ]
   Comparison of the average duration of operation between the groups
4. Duration of cardiopulmonary bypass [ Time Frame: During the aortic valve replacement surgery ]
   Comparison of the average duration of cardiopulmonary bypass between the groups
5. Duration of aortic clamping [ Time Frame: During the aortic valve replacement surgery ]
   Comparison of the average duration of aortic clamping between the two groups
6. Major Adverse Cardiac and Cerebrovascular Events (MACCE) [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 7 days ]
   A composite endpoint of mortality, myocardial infarction, urgent revascularization, stroke and major bleeding
7. Blood transfusion [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 7 days ]
   A comparison of the number of transfusions between the groups
8. Rethoracotomy for bleeding [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 7 days ]
   The incidence of rethoracotomy for bleeding after surgery
9. Post-operative pain [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 7 days ]
   Measurement of patient's subjective assessment of their pain after surgery using a visual scale
10. Duration of mechanical ventilation [ Time Frame: Measured from the time of arrival in the Intensive Care Unit until the time patients are extubated, an average of 12 hours ]
    Comparison of the average duration of mechanical ventilation between the groups
11. Length of ICU stay [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 30 days ]
    Comparison of the average number of days spent in Intensive Care Unit between the two groups
12. Length of hospital stay [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 30 days ]
    Comparison of the average number of days spent in hospital between the groups
13. Atrial fibrillation [ Time Frame: From the time of surgery until the patient is discharged from hospital, an average of 7 days ]
    Incidence of new-onset atrial fibrillation after cardiac surgery
14. Wound infection [ Time Frame: During the first 30 days after surgery ]
    Incidence of wound infections
15. Mortality [ Time Frame: During the first 30 days after surgery ]
    intra- and postoperative mortality

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Indication for elective isolated aortic valve replacement
• Anatomical suitability for both sternotomy and parasternal access
• Age ≥ 18
• Written informed consent in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria:

• Planned simultaneous cardiac surgery interventions (Mitral valve surgery, tricuspid valve surgery, CABG, Pacemaker or defibrillator implantation, Pulmonalvenenisolation, Maze, closure of left atrial appendage , patent foramen ovale or atrial septal defect closure)
• Acute myocardial infarction within 4 weeks, coronary heart disease
• Acute endocarditis
• TIA or stroke within 6 months prior to the procedure
• Pregnant or breast-feeding women
• Renal failure requiring dialysis
• Ejection fraction ≤ 30%
• Re-operation
• Disease with a life expectancy < 2 years
• Therapy with glucocorticoids or immunosuppressants

Contacts and Locations

Contacts

Contact: Sophie Tkebuchava, MD; +4936419322928; sophio.tkebuchava@med.uni-jena.de

Contact: Torsten Doenst, MD; +4936419322901; doenst@med.uni-jena.de

Locations

Germany

UKJ; Recruiting

Jena, Thueringen, Germany, 07747

Sponsors and Collaborators

Jena University Hospital

The German Heart Foundation

Investigators

• Principal Investigator: Sophie Tkebuchava, MD; University Hospital Jena
• Principal Investigator: Torsten Doenst, MD; University Hospital Jena

More Information

• Responsible Party: Jena University Hospital
• ClinicalTrials.gov Identifier: NCT04632095
• Other Study ID Numbers: PASTA-UKJ
• First Posted: November 17, 2020
• Last Update Posted: March 23, 2021
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Jena University Hospital:

Aortic Valve Stenosis; minimally invasive surgery; parasternal approach; quality of life; aortic valve replacement; inflammatory markers

Additional relevant MeSH terms:

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