Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension (DENERV'AP)

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Procedure: denervation; Procedure: sham procedure

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38700
    • CHU de Grenoble
  • Marseille, France, 13354
    • AP-HM
  • Nice, France, 06000
    • CHU de Nice
  • Toulouse, France, 31059
    • CHU de Toulouse
  • ¨Paris, France, 75015
    • AP-HP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: control group	Procedure: sham procedure; 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.
Experimental: denervation	Procedure: denervation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Collaborators: Assistance Publique - Hôpitaux de Paris; Assistance Publique Hopitaux De Marseille; University Hospital, Grenoble; University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2016
• Primary Completion (Actual): December 6, 2022
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: July 3, 2015
• First Submitted That Met QC Criteria: August 14, 2015
• First Posted (Estimated): August 18, 2015

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 14-APN-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO