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

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ClinicalTrials.gov Identifier: NCT02525926
Recruitment Status : Recruiting
First Posted : August 18, 2015
Last Update Posted : August 23, 2017
Assistance Publique Hopitaux De Marseille
University Hospital, Toulouse
University Hospital, Grenoble
Assistance Publique - Hôpitaux de Paris
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Pulmonary Arterial Hypertension Procedure: denervation Procedure: sham procedure

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension
Study Start Date : January 2016
Primary Completion Date : March 2017
Estimated Study Completion Date : September 2019

Arm Intervention/treatment
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.
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.

Primary Outcome Measures :
  1. Mean pulmonary artery pressure (in mmHg) measured during right heart catheterization [ Time Frame: at 6 month ]

Secondary Outcome Measures :
  1. Mean pulmonary artery pressure (in mmHg) from the initial procedure [ Time Frame: at 3 month ]
  2. Pulmonary vascular resistance (in Wood units) measured during right cardiac catheterization. [ Time Frame: at 6 month ]
  3. Clinical parameters: NYHA class [ Time Frame: at 6 month ]
  4. Clinical parameters: Borg dyspnea rating scale [ Time Frame: at 6 month ]
  5. Clinical parameters: 6-minute walk test (distance walked in meters), [ Time Frame: at 6 month ]
  6. Clinical parameters: oxygen dependence (quantity of oxygen in L/min), [ Time Frame: at 6 month ]
  7. Clinical parameters: ECG with supra ventricular arrhythmia. [ Time Frame: at 6 month ]
  8. Biological parameters: levels of Brain Natriuretic Peptide (pg/ml) in non-fasting morning samples. [ Time Frame: at 6 month ]
  9. Biological parameters: levels of troponin Ic (ng/ml) in non-fasting morning samples. [ Time Frame: at 6 month ]
  10. Echocardiographic parameters of right ventricular function [ Time Frame: 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

  11. Other hemodynamic parameters obtained by right cardiac catheterization [ Time Frame: at 6 month ]
    1. Cardiac index/output using thermodilution (L/min/m2)
    2. Right atrial pressure (mmHg)

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02525926

Contact: Vanina OLIVERI, PM 0033 4 92 03 40 11 drc@chu-nice.fr

CHU de Grenoble Active, not recruiting
Grenoble, France, 38700
AP-HM Not yet recruiting
Marseille, France, 13354
Principal Investigator: Jean Louis BONNET, PU-PH         
Sub-Investigator: Thomas CUISSET, PU-PH         
CHU de Nice Recruiting
Nice, France, 06000
Contact: Vanina OLIVERI, Project Manager    0033 4 92 03 42 54    oliveri.v@chu-nice.fr   
Principal Investigator: Emile FERRARI, PU-PH         
Sub-Investigator: Priscille BOUVIER, PH         
CHU de Toulouse Not yet recruiting
Toulouse, France, 31059
Principal Investigator: Jérome RONCALI, PU-PH         
Sub-Investigator: Laurent TETU, PH         
AP-HP Not yet recruiting
¨Paris, France, 75015
Principal Investigator: Marc SAPOVAL, PU-PH         
Sub-Investigator: Olivier SANCHEZ, PH         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Assistance Publique Hopitaux De Marseille
University Hospital, Toulouse
University Hospital, Grenoble
Assistance Publique - Hôpitaux de Paris

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT02525926     History of Changes
Other Study ID Numbers: 14-APN-02
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases