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
Overview
- Phase
- Phase 4
- Intervention
- PADN
- Conditions
- Pulmonary Arterial Hypertension
- Sponsor
- Nanjing First Hospital, Nanjing Medical University
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Pulmonary artery hypertension (PAH)- related events
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Shaoliang Chen, MD
Vice President
Nanjing First Hospital, Nanjing Medical University
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
Arms & Interventions
PADN + 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.
Intervention: PADN
PADN + 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.
Intervention: Sildenafil
sham PADN + sildenafil
The radiofrequency ablation catheter placed, no ablations.
Intervention: sham PADN
sham PADN + sildenafil
The radiofrequency ablation catheter placed, no ablations.
Intervention: Sildenafil
Outcomes
Primary Outcomes
Pulmonary artery hypertension (PAH)- related events
Time Frame: Baseline to month 6
Including all-cause death, lung transplantation, atrial septostomy, worsening of PAH, initiation of treatment with intravenous or subcutaneous prostacyclin
Secondary Outcomes
- Pulmonary Vascular Resistance(Baseline to month 6)
- Cardiac output(Baseline to month 6)
- Trans-pulmonary pressure gradient(Baseline to month 6)
- Pulmonary arterial pressure(Baseline to month 6)
- Diastolic pressure gradient(Baseline to month 6)
- Borg Dyspnea Index(Baseline to month 6)
- 6-minute walk distance(Baseline to month 6)
- Pulmonary arterial compliance(Baseline to month 6)
- New York functional class(Baseline to month 6)
- Right atrial pressure(Baseline to month 6)
- World Health Organization (WHO) Functional Class(Baseline to month 6)