Endomyocardial FibrosisRV-REPAIRNCT05090228
Right Ventricle Remodeling After Pulmonary Valve Replacement and Percutaneous Pulmonary Valve Insertion
An observational study of Endomyocardial Fibrosis and Pulmonary Valve Stenosis, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
This study investigates damage of the right cardiac chamber in adult patients with a congenital heart defect involving the pulmonary valve (the heart valve between the right cardiac chamber and the lungs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endomyocardial Fibrosis, Pulmonary Valve Stenosis, Pulmonary Valve Insufficiency
- How many people
- 26 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2016to 1 Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Adults with congenital heart disease with severe Pulmonary Insufficiency and/or Pulmonary Stenosis with an indication for PVR or PPVI.
Who may be able to join
- Individual should meet the European Society of Cardiology criteria for pulmonary valve intervention according to congenital heart disease guidelines.
- Individual has an indication for PVR or PPVI according to the local GUCH heart team
- Individual is ≥18 years of age.
- Individual agrees to have all study procedures performed, and is competent and willing to provide written informed consent to participate in this clinical study.
- Patients are acceptable candidates for PVR or PPVI treatment in accordance with manufacturer's instructions for use.
Who cannot join
- Individual is younger than 18 years of age.
- Individual has an estimated glomerular filtration rate (eGFR) of <30mL/min/1.73m2, using the MDRD (Modification of Diet in Renal Disease) calculation.
- Individual has any serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, haemophilia, significant anaemia).
- Individual is pregnant, nursing or planning to be pregnant.
- Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
- Individual is currently enrolled in an investigational drug or device trial.
Show all 11Show fewer
- Individual with any contraindications for MRI:
- The presence of implanted non-MRI-compatible cardiac pacemaker or implanted cardioverter defibrillator.
- Implanted electronic devices like cochlear implants and nerve stimulators.
- Patients who are unable to fit into the bore of the magnet.
- Claustrophobia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Right Ventricle REmodeling After Pulmonary vAlve Replacement and Percutaneous Pulmonary Valve InseRtion, a Functional and Histopathological Assessment
This study investigates damage of the right cardiac chamber in adult patients with a congenital heart defect involving the pulmonary valve (the heart valve between the right cardiac chamber and the lungs). The investigators want to investigate if novel, less invasive techniques are feasible to assess damage of this right cardiac chamber, to improve follow-up and timing of intervention (valve replacement) in this group of patients.
Read the detailed description
Rationale:
In congenital heart disease the right heart is often affected, in contrast to acquired heart disease where the left ventricle and left sided valves are most often affected. In congenital patients, the right heart problem is most common linked to dysfunction of the pulmonary valve. In these congenital patients, with defects such as Tetralogy of Fallot (ToF), Double Outlet Right Ventricle (DORV), Pulmonary Valve Atresia, and Ventricular Septum Defect (VSD), the primary origin of the problem are dysplastic Pulmonary Valves (PV) and Right Ventricle Outflow Tract Obstruction (RVOTO). Often these valves or obstructions are excised to be replaced directly or in a later stage. Until the end '90s common therapy was to cut out the pulmonary valve and leave patients without pulmonary valve for 10 to 20 years. This resulted in a pendular flow between right ventricle and pulmonary arteries. This works because the pulmonary vascular resistance is low and therefore inflow is easy. There is also a congenital group in which the primary problem was left sided, but a right-sided problem is created by therapy. Since 20 years the Ross procedure is used for congenital aortic valve stenosis. The pulmonary valve is used in childhood to replace the aortic valve, and needs to be replaced in adolescence by a homograft (graft with human donor valve).
In both these groups (repeat) pulmonary valve replacement is necessary, at some stage, with an open procedure; Pulmonary Valve Replacement (PVR) or catheter procedure; Percutaneous Pulmonary Valve Insertion (PPVI), a method available since 2000. Because these valves only last for 10 to 20 years, timing of intervention is very important.
The last 10 years efforts have been done to delineate the best moment for pulmonary valve replacement. The aim is to prevent right ventricular failure due to pressure overload (stenosis of homograft), volume overload (absence of PV after excision or insufficiency of homograft) or a combination of pressure- and volume-overload, which is believed to be most malignant. In the past emphasis was paid to onset of symptoms instead of preventing right ventricular damage. Because symptoms in right ventricular failure are linked to the 'point of no return' (when the right ventricle doesn't fully recover after pulmonary valve replacement), most likely a better strategy is to intervene before symptoms arise. To be able to make reliable criteria for valve replacement we need to better understand the anatomical and functional impairments of the right ventricle and link this to histopathological changes. The investigators believe myocardial fibrosis is correlated to this 'point of no return'. In the last decades knowledge concerning RV volumes and function, electrocardiographic and exercise capacity has grown. But, the relation between volumes, function and histopathology is missing.
Objective:
Primary objectives: to investigate functional and histopathological changes of the right ventricle before and after PVR or PPVI. To investigate if non-invasive assessment of RV-remodeling including CMR-T1rho mapping is possible and validate this with the golden standard of histopathology.
Secondary objectives: to investigate changes in parameters, using echocardiography, electrocardiography, biomarkers, exercise capacity and quality of life in patients undergoing PVR or PPVI.
- Keywords
- Right ventricle (reverse) remodeling (fibrosis), Right ventricle pressure overloading, Right ventricle volume overloading
- Medical subject headings
- Endomyocardial Fibrosis, Pulmonary Valve Stenosis, Pulmonary Valve Insufficiency, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PVR/PPVI | Adult patients with congenital heart disease (GUCH) undergoing pulmonary valve replacement (PVR) or percutaneous pulmonary valve insertion (PPVI). |
What is being measured
The primary outcome is the main question the study is designed to answer.
histopathology: percentage of fibrosis in biopsies.
endomyocardial biopsies performed during valve replacement RV endomyocardial biopsies performed during valve replacement procedure.
Measured: 6 months
T1 time in ms
CMR
Measured: before and 6 months after valve replacement
T1 rho time in ms
CMR
Measured: before and 6 months after valve replacement
Late gadolinium enhancement
CMR
Measured: before and 6 months after valve replacement
Secondary outcomes (4)
Echocardiographic parameters
Right ventricular strain-rate (1/s).
Measured: before valve replacement and direct post-intervention, 1month and 6 months post-intervention
Electrocardiographic sign of RV hypertrophy
Right axis deviation of +110° or more.
Measured: before and 6 months after valve replacement (ECG and Holter)
Biomarkers
Brain natriuretic peptide (pmol/L)
Measured: Before and 6 months after valve replacement
Quality of life SF-36
SF-36
Measured: before and 6 months after valve replacement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start1 Feb 2016
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endomyocardial FibrosisStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michiel Voskuil, MD, PhD, UMC Utrecht
- Investigators
- Michiel Voskuil, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05090228
- Sponsor's protocol ID
- NL53771.041.15
- Other IDs
- 15-448/M
- Acronym
- RV-REPAIR
- Status last verified
- Oct 2021
- First submitted
- 3 Dec 2015
- Last updated
- 22 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Right Ventricle REmodeling After Pulmonary vAlve Replacement and Percutaneous Pulmonary Valve InseRtion, a Functional and Histopathological Assessment
- ClinicalTrials.gov ID
- NCT05090228
- Acronym / sponsor ID
- RV-REPAIR / NL53771.041.15
- Keywords
- Right ventricle (reverse) remodeling (fibrosis), Right ventricle pressure overloading, Right ventricle volume overloading
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- 1 Feb 2016 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 22 Oct 2021 (actual)
- 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.
This study investigates damage of the right cardiac chamber in adult patients with a congenital heart defect involving the pulmonary valve (the heart valve between the right cardiac chamber and the lungs). The investigators want to investigate if novel, less invasive techniques are feasible to assess damage of this right cardiac chamber, to improve follow-up and timing of intervention (valve replacement) in this group of patients.
Detailed description
Rationale:
In congenital heart disease the right heart is often affected, in contrast to acquired heart disease where the left ventricle and left sided valves are most often affected. In congenital patients, the right heart problem is most common linked to dysfunction of the pulmonary valve. In these congenital patients, with defects such as Tetralogy of Fallot (ToF), Double Outlet Right Ventricle (DORV), Pulmonary Valve Atresia, and Ventricular Septum Defect (VSD), the primary origin of the problem are dysplastic Pulmonary Valves (PV) and Right Ventricle Outflow Tract Obstruction (RVOTO). Often these valves or obstructions are excised to be replaced directly or in a later stage. Until the end '90s common therapy was to cut out the pulmonary valve and leave patients without pulmonary valve for 10 to 20 years. This resulted in a pendular flow between right ventricle and pulmonary arteries. This works because the pulmonary vascular resistance is low and therefore inflow is easy. There is also a congenital group in which the primary problem was left sided, but a right-sided problem is created by therapy. Since 20 years the Ross procedure is used for congenital aortic valve stenosis. The pulmonary valve is used in childhood to replace the aortic valve, and needs to be replaced in adolescence by a homograft (graft with human donor valve).
In both these groups (repeat) pulmonary valve replacement is necessary, at some stage, with an open procedure; Pulmonary Valve Replacement (PVR) or catheter procedure; Percutaneous Pulmonary Valve Insertion (PPVI), a method available since 2000. Because these valves only last for 10 to 20 years, timing of intervention is very important.
The last 10 years efforts have been done to delineate the best moment for pulmonary valve replacement. The aim is to prevent right ventricular failure due to pressure overload (stenosis of homograft), volume overload (absence of PV after excision or insufficiency of homograft) or a combination of pressure- and volume-overload, which is believed to be most malignant. In the past emphasis was paid to onset of symptoms instead of preventing right ventricular damage. Because symptoms in right ventricular failure are linked to the 'point of no return' (when the right ventricle doesn't fully recover after pulmonary valve replacement), most likely a better strategy is to intervene before symptoms arise. To be able to make reliable criteria for valve replacement we need to better understand the anatomical and functional impairments of the right ventricle and link this to histopathological changes. The investigators believe myocardial fibrosis is correlated to this 'point of no return'. In the last decades knowledge concerning RV volumes and function, electrocardiographic and exercise capacity has grown. But, the relation between volumes, function and histopathology is missing.
Objective:
Primary objectives: to investigate functional and histopathological changes of the right ventricle before and after PVR or PPVI. To investigate if non-invasive assessment of RV-remodeling including CMR-T1rho mapping is possible and validate this with the golden standard of histopathology.
Secondary objectives: to investigate changes in parameters, using echocardiography, electrocardiography, biomarkers, exercise capacity and quality of life in patients undergoing PVR or PPVI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PVR/PPVI | – | –Adult patients with congenital heart disease (GUCH) undergoing pulmonary valve replacement (PVR) or percutaneous pulmonary valve insertion (PPVI). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with congenital heart disease with severe Pulmonary Insufficiency and/or Pulmonary Stenosis with an indication for PVR or PPVI.
Key inclusion criteria (5 listed)
- Individual should meet the European Society of Cardiology criteria for pulmonary valve intervention according to congenital heart disease guidelines.
- Individual has an indication for PVR or PPVI according to the local GUCH heart team
- Individual is ≥18 years of age.
- Individual agrees to have all study procedures performed, and is competent and willing to provide written informed consent to participate in this clinical study.
- Patients are acceptable candidates for PVR or PPVI treatment in accordance with manufacturer's instructions for use.
Key exclusion criteria (11 listed)
- Individual is younger than 18 years of age.
- Individual has an estimated glomerular filtration rate (eGFR) of <30mL/min/1.73m2, using the MDRD (Modification of Diet in Renal Disease) calculation.
- Individual has any serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, haemophilia, significant anaemia).
- Individual is pregnant, nursing or planning to be pregnant.
- Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
histopathology: percentage of fibrosis in biopsies.
Time frame: 6 months
endomyocardial biopsies performed during valve replacement RV endomyocardial biopsies performed during valve replacement procedure.
T1 time in ms
Time frame: before and 6 months after valve replacement
CMR
T1 rho time in ms
Time frame: before and 6 months after valve replacement
CMR
Late gadolinium enhancement
Time frame: before and 6 months after valve replacement
CMR
4 secondary outcomes
Echocardiographic parameters
Time frame: before valve replacement and direct post-intervention, 1month and 6 months post-intervention
Electrocardiographic sign of RV hypertrophy
Time frame: before and 6 months after valve replacement (ECG and Holter)
Biomarkers
Time frame: Before and 6 months after valve replacement
Quality of life SF-36
Time frame: before and 6 months after valve replacement
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2021.
Related trials for Endomyocardial Fibrosis
Active, not recruitingPhase 2
The COlchicine HypERtENsion Trial
Hypertension
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. This study is not recruiting at the moment.
Michiel Voskuil, MD, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Endomyocardial Fibrosis and Pulmonary Valve Stenosis, run by UMC Utrecht at 1 site in Netherlands.
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 11 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: finished, as of the sponsor's last update on 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
histopathology: percentage of fibrosis in biopsies. (time frame: 6 months). The study lists 4 primary outcomes in all. 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 22 Oct 2021.