Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary arterial hypertension
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.
Interventions
PROCEDUREPADN
Contrast pulmonary artery angiography is performed to localize the pulmonary artery bifurcation level and to calculate the PA diameter. Once the anatomy is deemed acceptable, the radiofrequency ablation catheter is introduced into the distal bifurcation area of the main PA. The catheter is then maneuvered within the PA to allow energy delivery to ensure that the electrodes are tightly in contact with the endovascular surface. 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.
PROCEDUREsham PADN
The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.
DRUGSildenafil
Participants initially received 5 mg tadalafil for the first 2 weeks in the two groups. The tadalafil dose may have been up titrated to 40 mg after 2 weeks, with maximum effects being obtained. The up titrated of tadalafil to 40 mg was not mandatory if the investigator decided for tolerability reasons the participants should remain on 5 mg.
Sponsors
Nanjing First Hospital, Nanjing Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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. |
| 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. |
| 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 pressure | Baseline to month 6 | Pulmonary arterial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration. |
| Right atrial pressure | Baseline to month 6 | Right atrial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration. |
| Pulmonary Vascular Resistance | Baseline to month 6 | PVR=\[mean pulmonary arterial pressure-pulmonary artery occlusion pressure\] / cardiac output |
| 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). |
| 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. |
| Pulmonary arterial compliance | Baseline to month 6 | Pulmonary arterial compliance was obtained with a 7-F flow-directed Swan-Ganz catheter. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The prognostic role of 18F-DOPA PET/CT in patients with PAH | 6 months | the prognostic role of 18F-DOPA PET/CT in patients with PAH. |
| Pulmonary artery perforation | During PADN procedure | Number of Participants with pulmonary artery perforation |
| Pulmonary embolism | 6 months | PE is classified by suspected and fatal ones. Suspected PE is defined as one of the following: 1) new intra-luminal filling defect on CT scan, MRI scan, or pulmonary angiogram; 2)new perfusion defect of at least 75% on V/Q lung scan; and 3) inconclusive spiral CT, pulmonary angiography or lung scan with demonstration of deep vein thrombosis in the lower extremities by venography. Fatal PE is PE based on objective diagnostic testing or autopsy or death not attributed to a documented cause and for which deep vein thrombosis/PE cannot be ruled out. |
Countries
China
Outcome results
None listed