Tricuspid DiseaseNOSTRUMNCT02996552
Annuloplasty for Not-Severe TR in Patients Undergoing MV Repair Versus Mitral Repair Only (NOSTRUM)
A study testing M & T Repair Group and Mitral-Only Group in people with Tricuspid Disease and Mitral Regurgitation, run by Ospedale San Raffaele at 3 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tricuspid Disease, Mitral Regurgitation
- What is being tested?
- M & T Repair Group and Mitral-Only Group
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 8 Jun 2011to Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- patient's refusal
- non-elective cardiac surgery;
- organic disease of tricuspid valve
- TR≥3
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Italy2 sites, 2 recruiting
- Recruiting
IRCCS Ospedale San Raffaele
Milan, 20132
Michele De Bonis, MD, 00390226437118, debonis.michele@hsr.it
Michele De Bonis, MD,FESC,FAHA
- Recruiting
Istituto Clinico Humanitas
Rozzano, Milano, 20089
Lucia Torracca, MD, 00390282244330, lucia.torracca@humanitas.it
Lucia Torracca, MD
Poland1 site, 1 recruiting
- Recruiting
Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
Warsaw, 02-507
Piotr Suwalski, MD, 0048225081260, suwalski.piotr@gmail.com
Piotr Suwalski, MD
About this study
Official title: 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.
Read more
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).
Read the 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:
- M \& T Repair Group
- 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.
- Conditions
- Tricuspid Disease, Mitral Regurgitation
- Being tested
- M & T Repair Group, Mitral-Only Group
- Keywords
- Tricuspid annulus dilation, mitral valve regurgitation
- Medical subject headings
- Mitral Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M & T Repair GroupProcedure or surgery
After the mitral valve repair a device for tricuspid annuloplasty will be implanted.
Mitral-Only GroupProcedure or surgery
Mitral valve repair alone; after the mitral valve repair no device for tricuspid annuloplasty will be implanted.
| Study group | Role | What they receive |
|---|---|---|
| M & T Repair Group | Experimental | Both mitral and tricuspid valves repair Receives: Procedure: M & T Repair Group |
| Mitral-Only Group | Active comparator | Only mitral valve repair Receives: Procedure: Mitral-Only Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
The 1-year freedom from recurrence of TR≥3+ and from progression by 2 degrees compared to pre-operative.
Measured: 1 year
Secondary outcomes (2)
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)
Measured: 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)
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2016 (estimated)
- Study start8 Jun 2011
- Primary completionJun 2020
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tricuspid DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 142 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- Istituto Clinico Humanitas, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
- Responsible party
- Principal investigator, Michele De Bonis, Ospedale San Raffaele
- Investigators
- Michele De Bonis, MD,FESC,FAHA, Principal investigator, IRCCS Ospedale San Raffale Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02996552
- Sponsor's protocol ID
- 072/11
- Acronym
- NOSTRUM
- Status last verified
- Jul 2020
- First submitted
- 6 Dec 2016
- Last updated
- 21 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Annuloplasty for the Treatment of Not-Severe Tricuspid Regurgitation in Patients Undergoing Surgery for Mitral Valve Disease: a Prospective, Spontaneous, Multicentre, Randomized Study
- ClinicalTrials.gov ID
- NCT02996552
- Acronym / sponsor ID
- NOSTRUM / 072/11
- Conditions
- Tricuspid Disease, Mitral Regurgitation
- Keywords
- Tricuspid annulus dilation, mitral valve regurgitation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 142 participants (estimated)
- Lead sponsor
- Ospedale San RaffaeleUniversity, hospital or other
- Collaborators
- Istituto Clinico Humanitas, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
- Study start
- 8 Jun 2011 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Dec 2030 (estimated)
- First posted
- 19 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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:
- M \& T Repair Group
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| M & T Repair Group | Experimental | Procedure: M & T Repair GroupBoth mitral and tricuspid valves repair |
| Mitral-Only Group | Active comparator | Procedure: Mitral-Only GroupOnly mitral valve repair |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- patient's refusal
- non-elective cardiac surgery;
- organic disease of tricuspid valve
- TR≥3
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M & T Repair GroupAfter the mitral valve repair a device for tricuspid annuloplasty will be implanted. | Procedure or surgery | M & T Repair Group |
| Mitral-Only GroupMitral valve repair alone; after the mitral valve repair no device for tricuspid annuloplasty will be implanted. | Procedure or surgery | Mitral-Only Group |
Primary outcome
The 1-year freedom from recurrence of TR≥3+ and from progression by 2 degrees compared to pre-operative.
Time frame: 1 year
2 secondary outcomes
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)
Time frame: 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)
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michele De Bonis, MD,FESC,FAHA principal investigator
IRCCS Ospedale San Raffale Milano
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing M & T Repair Group and Mitral-Only Group in people with Tricuspid Disease and Mitral Regurgitation, run by Ospedale San Raffaele at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michele De Bonis, MD,FESC,FAHA (00390226437118, debonis.michele@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The 1-year freedom from recurrence of TR≥3+ and from progression by 2 degrees compared to pre-operative. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2020.