BPA in CTEPD Without PH

BALLOON-TRIAL is a mono-center, prospective, open-label, randomized clinical trial with PROBE design. By adopting a cross-over part, all patients are eventually offered Balloon Pulmonary Angioplasty (BPA) treatment. In addition, this design allows assessment of several important secondary endpoints, such as the duration of the therapeutic effects of the intervention and the most appropriate timing of the intervention. Finally, this design minimizes the influence of confounding covariates, because each patient serves as his or her own control in the evaluation of several secondary endpoints.

As part of clinical care, persistent dyspnea and functional limitations (NYHA class ≥2) are routinely assessed at least three months after the index PE diagnosis. All symptomatic patients are subjected to routine blood testing including Hb, NT-proBNP and creatinine, resting transthoracic echocardiography, computed tomography pulmonary angiography (CTPA), perfusion imaging and/or pulmonary angiography (< 6 months), cardiopulmonary exercise testing (CPET) using a stationary cycle ergometer, Work Rate cycle Test (CWRT) and pulmonary function tests. Furthermore a right heart catheterization will be preferably performed in all patients.

Rehabilitation seems effective and safe in patients with acute PE and in patients with CTEPH, and can be considered standard of care for patients with chronic tromboembolic pulmonary disease (CTEPD) without pulmonary hypertension (PH). Because deconditioning is a known contributor to exercise intolerance after acute pulmonary embolism, patients need to have followed a rehabilitation program of at least 8 weeks before inclusion. Depending on the local protocol, rehabilitation sessions could be daily or a few times a week. Of note, if exercise tests are performed prior to rehabilitation, they should be repeated thereafter to evaluate the effect of rehabilitation, as part of clinical care. Subsequently, all test results are discussed in a multidisciplinary team of PH experts with specific expertise in CTEPH/CTEPD, including cardiologists, pulmonologists, (intervention) radiologists, cardiothoracic surgeons and vascular medicine specialists. Patients diagnosed with CTEPD with mPAP < 25mmHg and PVR < 3WU and who are eligible for this trial will be asked for informed consent for study participation. Of note, if no right heart catheterization is available at screening, patients can still be randomized and in case of a mPAP > 25mmHg, measured by the first BPA, patients will be excluded from the study. After signing informed consent, all PROMS are collected; all questionnaires are automatically distributed by mail and patients are asked to fill in and return digitally.

Patients will be randomized (ratio 1:1) between BPA versus standard of care, which is conservative treatment without specific intervention. Because recovery of symptoms may also occur spontaneously in CTEPD with PVR < 3, the study is controlled by the non-intervention arm. However, all participants will have the opportunity to undergo BPA by during the cross-over phase of the study. The cross-over will take place six months following randomization and after evaluating the primary and secondary outcomes. After the cross-over, patients subjected to the BPA arm will be followed for six months without any intervention. Vice versa, the other cohort will be subjected to BPA following the exact same treatment protocol. All patients will be followed for 24 months. Patients are asked to complete PROMS at randomisation and after 6, 12 and 24 months follow-up. Physical performance, measured by exercise tests will be assessed, in both study arms 6 and 12 months after randomization (and at least 2 months following the last BPA).

The study is unblinded to investigators and patients, but adjudication of the primary outcome measure and will be completed by a blinded committee.