Clinical trial NCT06209710: Balloon Pulmonary Angioplasty vs. Combined Approach With Pulmonary Artery Denervation in CTEPH: Effectiveness Comparison
Official title: Comparing Effectiveness of Balloon Pulmonary Angioplasty Alone vs. Combined With Pulmonary Artery Denervation in Chronic Thromboembolic Pulmonary Hypertension Patients Receiving Standard Medical Therapy
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
Conditions: Chronic Thromboembolic Pulmonary Hypertension
Keywords: Balloon pulmonary angioplasty
Pulmonary artery denervation
CTEPH
Lead sponsor: Military Medical Academy, Belgrade, Serbia
Sponsor class: OTHER
Collaborators: name: Military Medical Academy, Belgrade, Serbia
name: Galen Research
First posted: 2024-01-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention Group: Patients assigned to this group undergo a combination of Balloon Pulmonary Angioplasty (BPA) and Pulmonary Artery Denervation (PADN) alongside standard drug therapy.

Control Group: Patients in this group receive Balloon Pulmonary Angioplasty (BPA), Sham Pulmonary Denervation and standard drug therapy.
Primary purpose: TREATMENT

Brief summary: This clinical trial investigates new treatment approaches for chronic thromboembolic pulmonary hypertension (CTEPH), a condition affecting the lungs' blood vessels. CTEPH often develops after repeated blood clots in the lungs, leading to increased pressure and strain on the heart. The study aims to assess the effectiveness of combining two treatments, balloon pulmonary angioplasty (BPA) and pulmonary artery denervation (PADN), in reducing blood pressure in the lungs compared to the standard treatment. Additionally, the trial will explore the impact of these treatments on patients' quality of life. The hope is to improve outcomes and provide valuable insights into managing this challenging condition.

Detailed description: This clinical trial focuses on advancing our understanding and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH arises when blood clots in the lungs fail to fully dissolve, leading to the formation of fibrous masses that obstruct blood vessels, increase pulmonary blood pressure, and strain the heart's right ventricle.

The study's primary objective is to evaluate the combined use of two innovative treatments, Balloon Pulmonary Angioplasty (BPA) and Pulmonary Artery Denervation (PADN), in comparison to the standard treatment for CTEPH. BPA involves using a balloon to open narrowed or blocked pulmonary arteries, while PADN is a novel therapy targeting nerve clusters near the main pulmonary artery to reduce blood pressure.

The trial also aims to assess the impact of these treatments on patients' quality of life and clinical improvement measured through the 6-Minute Walk Test Distance (6-MWTD) and the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaires.In addition to evaluating the combined efficacy of BPA and PADN compared to standard treatment, this clinical trial has a specific objective to customize the PADN intervention based on individual patient characteristics. The study aims to determine the optimal number of radiofrequency (RF) ablation points required for effective PADN, considering the pulmonary artery size or diameter. This innovative approach seeks to tailor the intervention to the unique anatomical features of each patient, enhancing the precision and effectiveness of the treatment strategy.

The study design is a randomized parallel cohort study involving patients with CTEPH in phases 2/3. Patients are divided into two groups-intervention and control-and receive distinct treatment protocols. The intervention group undergoes a combination of BPA, PADN, and standard drug therapy, while the control group receives BPA, sham PADN intervention and standard drug therapy.

The BPA procedure involves accessing the pulmonary artery through the right femoral vein, measuring pressures, and selectively dilating stenosed or occluded branches. After the BPA procedure, PADN is performed by applying radiofrequency energy near the bifurcation of the main pulmonary artery.The sham PADN involves catheter placement mimicking the actual procedure without the application of radiofrequency energy.

The study includes detailed criteria for patient inclusion and exclusion, and patients are closely monitored through scheduled face-to-face visits. The trial plans to enroll approximately 20 patients.

Data management ensures the confidentiality of patient information, and analysis includes a descriptive approach and comparison of mPAP reduction after three months.

The study follows ethical guidelines, Good Clinical Practice, and recommendations from the European Association of Cardiology. Informed consent is a crucial aspect, and patient safety is paramount throughout the trial.

The trial's ultimate goal is to contribute valuable insights into the efficacy of combining BPA and PADN as a potential treatment strategy for CTEPH, aiming to improve patient outcomes and enhance our approach to managing this complex condition.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Age 18 - 80 years.
* Diagnosis of chronic thromboembolic heart disease.
* Mean pulmonary arterial pressure (mPAP) \>20 mmHg.
* Pulmonary vascular resistance \>3 Wood units.
* Presence of organized thrombus masses.
* World Health Organization (WHO) functional class II to IV.

Exclusion Criteria:

* Proximal organized thrombotic masses not suitable for Balloon Pulmonary Angioplasty (BPA) and Pulmonary Artery Denervation (PADN).
* WHO functional class I

Additionally, participants can be excluded from the trial under the following circumstances:

* Withdrawal of consent at any time.
* Failure to complete the treatment as per protocols.
* Protocol violations.

Primary outcomes:
measure: Change in mean Pulmonary Arterial Pressure (mPAP)
timeFrame: 3 months
Secondary outcomes:
measure: Quality of Life Assessment
timeFrame: 3 months, and 1 year
measure: Physical Functionality Assessment
timeFrame: 3 months, and 1 year
measure: Hemodynamic Response Assessment
timeFrame: 1 year
measure: Adverse Events
timeFrame: 3 months, abd 1 year
measure: Survival Rates
timeFrame: 1 year
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: Military Medical Academy
Study officials:
affiliation: Clinic of Cardiology, Military Medical Academy, Belgrade, Serbia
name: Slobodan Obradovic, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen SL, Zhang FF, Xu J, Xie DJ, Zhou L, Nguyen T, Stone GW. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol. 2013 Sep 17;62(12):1092-1100. doi: 10.1016/j.jacc.2013.05.075. Epub 2013 Jul 10.
citation: Zhang H, Wei Y, Zhang C, Yang Z, Kan J, Gu H, Fan F, Gu H, Wang Q, Xie D, Zhang G, Guo X, Yin Y, Jin B, Zhou H, Yang Z, Wang Z, Xin Y, Zhang C, Meng L, Wang X, Sun J, Zhao C, Zhang J, Yan X, Chen F, Yao C, Stone GW, Chen SL. Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial. JACC Cardiovasc Interv. 2022 Dec 12;15(23):2412-2423. doi: 10.1016/j.jcin.2022.09.013. Epub 2022 Sep 18.