Clinical Research Directory

Berlin Registry of Right Heart Interventions

The present study evaluates patients after interventional therapy of valvular diseases of the right heart. Follow-up examinations include medical history taking, laboratory measurements and an echo. The aim is to assess the different interventional therapies and their impact on patient's outcome.

Harmony TPV Post-Approval Study

The purpose of this study is to characterize the functionality of transcatheter implantation of the Medtronic Harmony Transcatheter Pulmonary Valve (TPV) achieved by real-world implanters.

ALTERRA Post-Approval Study

This study will monitor device performance and outcomes in subjects undergoing implantation of the Edwards SAPIEN 3 Transcatheter Pulmonary Valve System with Alterra Adaptive Prestent in the post-approval setting

ALTERRA: SAPIEN 3 THV With the Alterra Adaptive Prestent

To demonstrate the safety and effectiveness of the Edwards Alterra Adaptive Prestent in conjunction with the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) System in subjects with a dysfunctional right ventricular outflow tract/pulmonary valve (RVOT/PV) who are indicated for treatment of pulmonary regurgitation (PR). Following completion of enrollment, subjects will be eligible for enrollment in the continued access phase of the trial.

The Medtronic Harmony™ Transcatheter Pulmonary Valve Clinical Study

The purpose of this study is to further evaluate the safety and effectiveness of the Harmony™ TPV system. The Pivotal/CAS phases of the study have transitioned into a post-approval study to confirm the long-term functionality of transcatheter implantation of the Medtronic Harmony TPV.

Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial

Repaired Tetralogy of Fallot (rTOF) is the leading cause of congenital cyanotic heart disease worldwide, involving up to 7-10% of congenital heart disease. With advances in open-heart surgical repair techniques and medical therapies, there is a significant increase in patients with rTOF surviving till late adulthood. One sequalae that nearly all rTOF patients develop during their lifetime is significant pulmonary regurgitation. Pulmonary regurgitation causes progressive right ventricular dilatation and systolic dysfunction, which in turn impairs cardio-pulmonary function and overall survival. There is currently no pharmacological therapy proven to improve cardio-pulmonary function in rTOF patients. In a double-blind, placebo controlled, randomized controlled trial involving 33 rTOF patients, the use of beta-adrenergic receptor blocker Bisoprolol failed to improve maximal oxygen uptake (VO2 max) in the treatment group. Furthermore, there was no significant change in dimension of right ventricle on cardiac imaging, or heart failure biomarkers including brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). In the APPROPRIATE trial involving 64 patients, angiotensin-converting-enzyme inhibitor (ACEI) Ramipril similarly failed to improve VO2 max despite an improved right ventricular long-axis shortening. In REDEFINE trial, 95 rTOF patients were randomized in to receive angiotensin receptor blocker (ARB) Losartan and control. At the end of study, there was no significant difference between the two groups in VO2 max, right ventricular ejection fraction, and other key outcomes. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a promising therapy for rTOF patients. Clinical trials consistently demonstrated that SGLT2 inhibitors reduce heart failure hospitalization and mortality among patients with heart failure with or without diabetes mellitus. There have been growing body of evidence that demonstrate that SGLT2 inhibitors improve right ventricular function. In a preclinical study of rat with pulmonary hypertension induced right ventricular failure, empagliflozin was found to reduce pulmonary pressure, alleviate right ventricular hypertrophy and reduce myocardial fibrosis. In a pilot study involving 10 patients with adult congenital heart disease and systemic right ventricular failure, SGLT2 inhibitors improved cardio-pulmonary function as reflected by 6-minute walk test performance and New York Heart Association functional status. Most recently, investigators from DAPA-SERVE randomized controlled trial reported that among 92 patients with systemic right ventricular failure, those randomized to receive SGLT2 inhibitors had superior systemic right ventricular function with larger fractional area change (FAC) and more negative free-wall global longitudinal strain. Nevertheless, as these trials involve patients with right ventricular connections to the systemic circulation rather than pulmonary circulation in rTOF, it is uncertain whether the trial results can be extrapolated to the rTOF population. The critical knowledge gap our proposed randomized controlled trial seeks to address is whether SGLT2 inhibitors improve cardio-pulmonary function in rTOF patients.

VenusP-Valve Pivotal Study (PROTEUS STUDY)

A prospective, multi-center, non-randomized interventional study to evaluate the safety and effectiveness of the VenusP-ValveTM System in patients with native right ventricular outflow tract (RVOT) dysfunction. Post procedure, a clinical visit will be scheduled at pre-discharge, 30 days, 6 months, 12 months, and annually thereafter to 10 years. About 60 subjects will be enrolled in this study. Data analysis will be performed after all enrolled subjects complete 6-month follow-up and the primary endpoint analysis report will be submitted to FDA for PMA approval.

Early Versus Later Re-valving in Tetralogy of Fallot With Free Pulmonary Regurgitation

Tetralogy of Fallot (ToF) is a congenital heart defect with four major features including right ventricular outflow tract obstruction. About 25 children are born with this condition in Denmark every year. Corrective surgery is usually performed within the first year. In 50 % of patients, enlargement with a patch is necessary to achieve relief of the outflow tract obstruction. This however results in severe pulmonary regurgitation, which eventually leads to volume overload, right ventricular dysfunction and arrhythmia. To avoid these late complications, pulmonary valve replacement with a prosthesis if performed when patients meet the current guideline criteria. Most patients meet the guideline criteria for revalving when they are between 20 and 30 years of age. The current guidelines however, are based solely on retrospective studies and novel research reveals that in more than 50 % of patients who are treated according to current practice, right ventricular volumes and function as well as exercise capacity and burden of arrhythmia do not normalize or improve. 500 patients with ToF will be enrolled in a multicentre, cross-sectional study, which will yield information about the long-term outcomes after initial repair of ToF, as well as suggestions about the optimal timing for re-valving. Among patients included in the cross-sectional study, 120 patients with free pulmonary regurgitation, will be randomized evenly for early or later re-valving with at least 10-years of follow-up, for evaluation of long-term efficacy and safety of early re-valving.