Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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Pulmonary hypertension is a rare condition that leads to right ventricular dysfunction and premature death. Only modest improvements of outcomes have been observed with the current available advanced specific drug therapy. Pulmonary hypertension advanced therapy is also expensive and leads to frequent adverse effects, sometimes serious. Results from a pilot study, the first-in-man experience of pulmonary artery denervation, demonstrated a clinical improvement in 13 patients with severe pulmonary hypertension despite optimal medical management. However this single non-randomized study requires confirmation. The investigators propose a prospective multi-center, randomized, single-blinded trial. Its main objective will be to assess, in patients with uncontrolled pulmonary hypertension despite optimal medical management, the efficacy of pulmonary artery denervation in reducing mean pulmonary artery pressure (mPAP) at six months, compared to continued medical treatment following a simulated (sham) procedure. The principal evaluation criteria will be the mPAP change (in mm Hg) as measured by right heart catheterization. The study will run for 18 months and it will be necessary to recruit 50 patients. All adult patients (with the exception of pregnant women and individuals unable to receive an appropriate information and to give their free and informed consent) with uncontrolled pulmonary arterial hypertension despite optimal medical management will be invited to participate, in the absence of any exclusion criteria. The investigators will also measure changes in clinical, biological, echocardiographic and hemodynamic prognostic markers in both groups.

Official Title
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Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Procedure: denervation
* Procedure: sham procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pulmonary artery hypertension (group 1 of the Nice classification of pulmonary hypertension) Aged over 18 years old NYHA class III or IV Not controlled by optimal medical management as defined by: dual therapy including a prostacyclin. or dual therapy including an endothelin receptor antagonist and a 5-phosphodiesterase inhibitors, in patients with contra-indication of prostacyclin, poor tolerance to this treatment, prostacyclin derivative treatment failure or patient refusal. Valid status in the social security system Signed informed consent Exclusion Criteria: Patient eligible for pulmonary transplantation Pregnancy or breastfeeding Adults of the age of majority subject to guardianship court order or deprived of liberty Patient with history of radio frequency procedure Known heparin allergy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: denervation<br> | Procedure: denervation<br>* The examination proceeds under rigorous aseptic technique. Femoral, jugular or brachial venous access will be performed. A flexible catheter is first introduced across a 7-Fr venous introducer, and passed through the right heart chambers toward the origin of the pulmonary arteries. The pressures in the right heart chambers and the pulmonary artery will be measured. At the end of the examination, the catheter is removed, a dressing is applied and the venous puncture is compressed by hand.<br>|
| Sham Comparator: control group<br> | Procedure: sham procedure<br>* Right heart catheterism is mandatory in PAH patients care (for diagnosis and during follow-up) and will serve as a  sham  procedure. A usually performed and after a venous punction, cardiac outpout and pulmonary artery pressures will be recorded. Acoustically isolated headphones will be given to patients during the procedure in order to assure simple-blind during the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean pulmonary artery pressure (in mmHg) measured during right heart catheterization |  | at 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean pulmonary artery pressure (in mmHg) from the initial procedure |  | at 3 month | 
| Pulmonary vascular resistance (in Wood units) measured during right cardiac catheterization. |  | at 6 month | 
| Clinical parameters: NYHA class |  | at 6 month | 
| Clinical parameters: Borg dyspnea rating scale |  | at 6 month | 
| Clinical parameters: 6-minute walk test (distance walked in meters), |  | at 6 month | 
| Clinical parameters: oxygen dependence (quantity of oxygen in L/min), |  | at 6 month | 
| Clinical parameters: ECG with supra ventricular arrhythmia. |  | at 6 month | 
| Biological parameters: levels of Brain Natriuretic Peptide (pg/ml) in non-fasting morning samples. |  | at 6 month | 
| Biological parameters: levels of troponin Ic (ng/ml) in non-fasting morning samples. |  | at 6 month | 
| Echocardiographic parameters of right ventricular function | Right ventricular diameter at admission (mm) in 4-chamber view Right ventricular systolic function: tricuspid annular plane systolic excursion (TAPSE) (mm), peak S-wave velocity at the lateral tricuspid ring (cm/s), Right ventricular fractional area change (%), acceleration (m/s2) and peak isovolumic contraction (cm/s), pulmonary systolic time velocity integral (cm), longitudinal deformation of right ventricular free wall using speckle-tracking imaging (%) Right ventricular adaptation: right ventricular Tei-index and presence of pericardial effusion | at 6 month | 
| Other hemodynamic parameters obtained by right cardiac catheterization | Cardiac index/output using thermodilution (L/min/m2) Right atrial pressure (mmHg) | at 6 month |