Clinical trial NCT02284737: A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
Official title: A Prospective, Multi-center, Randomized Control Trial to Investigate the Efficacy of Pulmonary Artery Denervation to Improved Functional Capacity and Hemodynamics in Patients With Pulmonary Artery Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary arterial hypertension
Lead sponsor: Nanjing First Hospital, Nanjing Medical University
Sponsor class: OTHER
First posted: 2014-11-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Pulmonary artery hypertension (PAH)- related events
timeFrame: Baseline to month 6
Secondary outcomes:
measure: 6-minute walk distance
timeFrame: Baseline to month 6
measure: Pulmonary arterial pressure
timeFrame: Baseline to month 6
measure: Right atrial pressure
timeFrame: Baseline to month 6
measure: Pulmonary Vascular Resistance
timeFrame: Baseline to month 6
measure: Cardiac output
timeFrame: Baseline to month 6
measure: Trans-pulmonary pressure gradient
timeFrame: Baseline to month 6
measure: Diastolic pressure gradient
timeFrame: Baseline to month 6
measure: Pulmonary arterial compliance
timeFrame: Baseline to month 6
measure: Borg Dyspnea Index
timeFrame: Baseline to month 6
measure: World Health Organization (WHO) Functional Class
timeFrame: Baseline to month 6
measure: New York functional class
timeFrame: Baseline to month 6
Other outcomes:
measure: Pulmonary artery perforation
timeFrame: During PADN procedure
measure: Pulmonary embolism
timeFrame: 6 months
measure: The prognostic role of 18F-DOPA PET/CT in patients with PAH
timeFrame: 6 months
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
Study officials:
affiliation: Nanjing First Hospital, Nanjing Medical University, China
name: Shao-Liang Chen, MD
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: Chen SL, Zhang YJ, Zhou L, Xie DJ, Zhang FF, Jia HB, Wong SS, Kwan TW. Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo. EuroIntervention. 2013 Jun 22;9(2):269-76. doi: 10.4244/EIJV9I2A43.