Annuloplasty for Not-Severe TR in Patients Undergoing MV Repair Versus Mitral Repair Only (NOSTRUM) (NOSTRUM)

Annuloplasty for the Treatment of Not-Severe Tricuspid Regurgitation in Patients Undergoing Surgery for Mitral Valve Disease: a Prospective, Spontaneous, Multicentre, Randomized Study

The surgical treatment of less than severe (≤2+/4+) functional tricuspid regurgitation (TR) in patient undergoing mitral valve surgery, is still controversial: some observational studies have suggested that performing tricuspid annuloplasty in patients undergoing mitral valve surgery with a dilated tricuspid annulus, and TR≤2+ may provide a clinical benefit, while in other observational studies such benefit has not been documented.

The ESC Guidelines assign the class IIa recommendation for surgical treatment in patients with tricuspid regurgitation ≤2+ and a dilated annulus, if surgery is concomitant to the repair or replacement of the mitral valve. However the level of evidence C (expert opinion) confirms the absence of clear scientific evidence to support this recommendation.

It is therefore very important to carry out randomized trials designed to really prove the supposed efficacy of prophylactic tricuspid annuloplasty, especially in patients with degenerative etiology where the data are particularly controversial.

The aim of the study will be to establish the effectiveness of the tricuspid annuloplasty in the early stage of TR. The investigators enrolled patients with TR≤2+ and annular dilation undergoing mitral valve repair.

Primary end-point will be the freedom from recurrence of TR≥3+ and from progression of 2 degrees of TR compared to pre-operative, at discharge and 12 months after surgery, assessment by transthoracic echocardiography. Secondary endpoints are to demonstrate the superiority of combined treatment (M & T Repair Group) compared to single treatment (Mitral-Only Group) at 5 and 10 years after surgery.

This will be an experimental superiority, prospective, spontaneous, multicenter, randomized trial.

Patients will be randomly assigned to two parallel arms with an allocation ratio 1:1 stratified by center, to receive mitral repair only (Mitral-Only group) or both mitral and tricuspid repair (M & T Repair group).

Study Overview

• Status: Recruiting
• Conditions: Mitral Regurgitation; Tricuspid Disease
• Intervention / Treatment: Procedure: M & T Repair Group; Procedure: Mitral-Only Group

Detailed Description

Current guidelines recommend surgical treatment of secondary tricuspid regurgitation (TR) in patients with mild or moderate TR undergoing mitral valve (MV) surgery if significant dilatation of the tricuspid annulus is documented. Indeed, several observational series and small randomized studies have shown that in the presence of tricuspid annulus dilatation, not treating less than severe secondary TR may lead to progression of the tricuspid disease despite correction of the associated left-sided lesion.

However, the level of evidence C (expert opinion) confirms the absence of clear scientific evidence to support this recommendation.

It is therefore very important to carry out randomized trials designed to really prove the supposed efficacy of prophylactic tricuspid annuloplasty, especially in patients with degenerative etiology where the data are particularly controversial.

The aim of the study will be to establish the effectiveness of the tricuspid annuloplasty in the early stage. The investigators enrolled patient with TR≤2+ and annular dilation undergoing mitral valve repair.

This will be a multicenter single-blind parallel group randomized controlled trial. Patients will be randomly assigned to two parallel arms with an allocation ratio 1:1, to receive one of two surgical procedures. Patients that will match the inclusion criteria at the preoperative evaluation will be recruited.

Patient will be randomized according to a computer-generated list of casual numbers. Information about patient allocation will be kept in closed opaque envelopes and nobody will know patient allocation before randomization. Patients will be blind to allocation.

The day of surgery patients will be subsequently randomized into two arms with an allocation ratio 1:1 stratified by center, to receive:

1. M & T Repair Group
2. Mitral-Only Group Each group will consist of 71 patients. All patients will receive the mitral valve repair and in patients enrolled in the M & T Repair Group an Edwards MC3 Tricuspid ring will be implanted.

Primary end-point will be the freedom from recurrence of TR≥3+ and from progression of 2 degrees of TR compared to pre-operative, at discharge and 12 months after surgery, assessment by transthoracic echocardiography. Secondary endpoints are to demonstrate the superiority of combined treatment (M & T Repair Group) compared to single treatment (Mitral-Only Group) at 5 and 10 years after surgery.

For statistical analysis the data will be expressed as "average ± standard deviation" or as percentage. A "probability value" less than 0.05 will be considered as "statistically significant." Outcomes will be compared using the "X2" analysis for categorical variables and the "t-test" for the continuous onces. The data will be analyzed using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA) for Windows (Microsoft Corp, Redmond, WA). Survival and freedom from reoperation, freedom from TR≥3+ or from a progression of TR of at least 2 grades (as compared to baseline), will be analyzed by the method of Kaplan-Meier. The analysis "univariate" and possibly "multivariate" of risk factors will be performed with "Cox proportional hazards regression".

The Fine and Gray model will be used in a "competing risk analysis" for "time to TR ≥ 3+/4+" and "time to TR progression of at least 2 grades compared to baseline" considering the death event as competitive risk.

In addition, estimates of the respective cumulative incidence (CIF) of these events in the 2 groups will be compared to determine the impact on such endpoints of the execution or non-execution of tricuspid anuloplasty.

The aim of the study is to demonstrate the superiority of combined mitral and tricuspid treatment (M & T Repair) compared to isolated mitral repair (Mitral-Only Group) in the enrolled patients.

The primary end-point is to demonstrate that, at 1 year of follow-up, the recurrence of TR≥3+ or the progression of TR of at least 2 degrees (compared to baseline) occurs in less than 1% of the patients undergoing both mitral e tricuspid repair (M & T Repair Group). The expected rate for the Mitral-Only group is 15%. (Power = 80%, alpha = 0.05, Number of Patients per group = 71).

Secondary endpoints are to demonstrate the superiority of the combined treatment (M & T Repair Group) compared to the single treatment (Mitral-Only Group) at 5 and 10 years after surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 142
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michele De Bonis, MD,FESC,FAHA; Phone Number: 00390226437118; Email: debonis.michele@hsr.it
• Study Contact Backup: Name: Cinzia Trumello, MD; Phone Number: 00390226437127; Email: trumello.cinzia@hsr.it

Study Locations

• Italy
  • Milan, Italy, 20132
    • Recruiting
    • IRCCS Ospedale San Raffaele
    • Contact: Michele De Bonis, MD; Phone Number: 00390226437118; Email: debonis.michele@hsr.it
    • Principal Investigator: Michele De Bonis, MD,FESC,FAHA
    • Sub-Investigator: Cinzia Trumello, MD
    • Sub-Investigator: Teodora Nisi, MD
    • Sub-Investigator: Elisabetta Lapenna, MD
    • Sub-Investigator: Ottavio Alfieri, MD
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
      • Contact: Lucia Torracca, MD; Phone Number: 00390282244330; Email: lucia.torracca@humanitas.it
      • Principal Investigator: Lucia Torracca, MD
      • Sub-Investigator: Andrea Fumero, MD
• Poland
  • Warsaw, Poland, 02-507
    • Recruiting
    • Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
    • Contact: Piotr Suwalski, MD; Phone Number: 0048225081260; Email: suwalski.piotr@gmail.com
    • Principal Investigator: Piotr Suwalski, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• age > 18 years;
• ability to provide informed consent;
• patients scheduled for mitral valve regurgitation
• TR ≤ 2+ with annular dilation
• Tricuspid diastolic diameter ≥ 40 mm or 21 mm/m2

Exclusion Criteria:

• patient's refusal
• non-elective cardiac surgery;
• organic disease of tricuspid valve
• TR≥3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M & T Repair Group; Both mitral and tricuspid valves repair	Procedure: M & T Repair Group; After the mitral valve repair a device for tricuspid annuloplasty will be implanted.
Active Comparator: Mitral-Only Group; Only mitral valve repair	Procedure: Mitral-Only Group; Mitral valve repair alone; after the mitral valve repair no device for tricuspid annuloplasty will be implanted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The 1-year freedom from recurrence of TR≥3+ and from progression by 2 degrees compared to pre-operative.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The 5-year freedom from recurrence of TR >= 3+ and from progression by 2 degrees compared to pre-operative, in the combined treatment group (M & T Repair Group) and in the single treatment group ( Mitral-Only Group)	5 years
The 10-year freedom from recurrence of TR >= 3+ and from progression by 2 degrees compared to pre-operative, in the combined treatment group (M & T Repair Group) and in the single treatment group ( Mitral-Only Group)	10 years

Collaborators and Investigators

• Sponsor: Ospedale San Raffaele
• Collaborators: Istituto Clinico Humanitas; Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
• Investigators: Principal Investigator: Michele De Bonis, MD,FESC,FAHA, IRCCS Ospedale San Raffale Milano

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2011
• Primary Completion (Actual): June 1, 2020
• Study Completion (Anticipated): December 1, 2030

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: mitral valve regurgitation; Tricuspid annulus dilation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: 072/11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No