Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension

Not Applicable

Terminated

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Procedure: denervation; Procedure: sham procedure

• Registration Number: NCT02525926
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-07-03
• Study First Submitted QC: 2015-08-14
• Study First Posted: 2015-08-18
• Study Start: 2016-02-04
• Primary Completion: 2022-12-06
• Status Verified: 2024-10
• Study Completion: 2024-10-17
• Last Update Submitted: 2024-10-17
• Last Update Posted: 2024-10-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
denervation	denervation	-
control group	sham procedure	-

Primary Outcome Measures

Name	Time	Method
Mean pulmonary artery pressure (in mmHg) measured during right heart catheterization	at 6 month

Secondary Outcome Measures

Name	Time	Method
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: 6-minute walk test (distance walked in meters),	at 6 month
Clinical parameters: Borg dyspnea rating scale	at 6 month
Clinical parameters: oxygen dependence (quantity of oxygen in L/min),	at 6 month
Biological parameters: levels of Brain Natriuretic Peptide (pg/ml) in non-fasting morning samples.	at 6 month
Other hemodynamic parameters obtained by right cardiac catheterization	at 6 month	1. Cardiac index/output using thermodilution (L/min/m2); 2. Right atrial pressure (mmHg)
Clinical parameters: ECG with supra ventricular arrhythmia.	at 6 month
Echocardiographic parameters of right ventricular function	at 6 month	1. Right ventricular diameter at admission (mm) in 4-chamber view; 2. 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 (%); 3. Right ventricular adaptation: right ventricular Tei-index and presence of pericardial effusion
Clinical parameters: NYHA class	at 6 month
Biological parameters: levels of troponin Ic (ng/ml) in non-fasting morning samples.	at 6 month

Trial Locations

Locations (5)

AP-HP; 🇫🇷 ¨Paris, France

CHU de Grenoble; 🇫🇷 Grenoble, France

CHU de Toulouse; 🇫🇷 Toulouse, France

AP-HM; 🇫🇷 Marseille, France

CHU de Nice; 🇫🇷 Nice, France