A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Registration Number
- NCT02284737
- Brief Summary
Pulmonary arterial hypertension (PAH) is characterized by premature death mainly because of progressive and severe right ventricular failure. Target drugs are reported to be associated with significant improvement of clinical outcome for PAH patients. However, previous studies using those target drugs focused on the change of 6-minute walk distance (6MWD) and or hemodynamic responses. As 6MWD has weak correlation with clinical outcome (time to clinical worsening, TTCW), benefits from target drugs for PAH patients are not clear. We previously reported the safety and efficacy of pulmonary artery denervation (PADN) for treatment of PAH patients who were unresponsive to target drugs. Hence, we design the randomized study to identify the effect of PADN on PAH.
- Detailed Description
The current study is designed as a multicenter, randomized and prospective study aiming to compare the effect of PADN on PAH patients. Based on the previous studies, the rate of pulmonary arterial hypertension (PAH)-related event was around 30% after 6-month treatment using target drugs. And our previous data showed that this PAH-related event at 6-month after PADN procedure was 15%. As a result, a total of 270 PAH patients was required, with 135 patients/per group at a ratio of 1:1 randomization. All patients underwent an 18F-DOPA PET/CT scan of pulmonary arteries and the heart, performed at basement.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 100
- Provision of informed consent prior to any study specific procedures;
- Men and women 18 years and older;
- Group I PAH, defined as a mPAP≥25mmHg, PCWP<15mmHg and PVR[The PVR =(mPAP-PCWP)/CO]>3.0 Woods unit.
General exclusion criteria:
- Pregnancy and breast feeding mother;
- Estimated life expectancy <12 months;
- Scheduled major surgery in the next 6 months;
- Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk;
- Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 30 days.
Procedural exclusion criteria:
- WHO group II, III, IV, V PH
- Severe Renal dysfunction (Ccr<30 ml/min)
- Blood platelet count<100,000/L
- Expected life span<6-month
- Systematical inflammation
- Malignant cancer(s)
- Tricuspid valve stenosis, Supra-pulmonary valve stenosis
- Allergic to studied drugs or metal materials.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PADN + sildenafil PADN Two to three ablations at 1-15 W for 120 seconds at each point were performed in the distal bifurcation area of the main PA. sham PADN + sildenafil sham PADN The radiofrequency ablation catheter placed, no ablations. PADN + sildenafil Sildenafil Two to three ablations at 1-15 W for 120 seconds at each point were performed in the distal bifurcation area of the main PA. sham PADN + sildenafil Sildenafil The radiofrequency ablation catheter placed, no ablations.
- Primary Outcome Measures
Name Time Method Pulmonary artery hypertension (PAH)- related events Baseline to month 6 Including all-cause death, lung transplantation, atrial septostomy, worsening of PAH, initiation of treatment with intravenous or subcutaneous prostacyclin
- Secondary Outcome Measures
Name Time Method Pulmonary Vascular Resistance Baseline to month 6 PVR=\[mean pulmonary arterial pressure-pulmonary artery occlusion pressure\] / cardiac output
Cardiac output Baseline to month 6 The amount of blood the heart pumps through the circulatory system in a minute. Measured by right heart catheterization.
Trans-pulmonary pressure gradient Baseline to month 6 The transpulmonary pressure gradient (TPG), defined by the difference between mean pulmonary arterial pressure (P(pa)) and left atrial pressure (P(la).
Pulmonary arterial pressure Baseline to month 6 Pulmonary arterial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration.
Diastolic pressure gradient Baseline to month 6 The diastolic pressure gradient (DPG), defined by the difference between mean pulmonary arterial pressure and PA occlusion pressure.
Borg Dyspnea Index Baseline to month 6 Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
6-minute walk distance Baseline to month 6 The 6-minute walk distance (6MWD) test was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.).
Pulmonary arterial compliance Baseline to month 6 Pulmonary arterial compliance was obtained with a 7-F flow-directed Swan-Ganz catheter.
New York functional class Baseline to month 6 NYHA Classes: I) Patients with no limitation of activities; they suffer no symptoms from ordinary activities. II) Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion. III) Patients with marked limitation of activity; they are comfortable at rest. IV) Patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.
Right atrial pressure Baseline to month 6 Right atrial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration.
World Health Organization (WHO) Functional Class Baseline to month 6 WHO Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possible at rest.
Trial Locations
- Locations (1)
Nanjing First Hospital
🇨🇳Nanjing, Jiangsu, China