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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
denervation
sham procedure
Sponsored by
Centre Hospitalier Universitaire de Nice
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de Grenoble
  • AP-HM
  • CHU de Nice
  • CHU de Toulouse
  • AP-HP

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

denervation

control group

Arm Description

Outcomes

Primary Outcome Measures

Mean pulmonary artery pressure (in mmHg) measured during right heart catheterization

Secondary Outcome Measures

Mean pulmonary artery pressure (in mmHg) from the initial procedure
Pulmonary vascular resistance (in Wood units) measured during right cardiac catheterization.
Clinical parameters: NYHA class
Clinical parameters: Borg dyspnea rating scale
Clinical parameters: 6-minute walk test (distance walked in meters),
Clinical parameters: oxygen dependence (quantity of oxygen in L/min),
Clinical parameters: ECG with supra ventricular arrhythmia.
Biological parameters: levels of Brain Natriuretic Peptide (pg/ml) in non-fasting morning samples.
Biological parameters: levels of troponin Ic (ng/ml) in non-fasting morning samples.
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
Other hemodynamic parameters obtained by right cardiac catheterization
Cardiac index/output using thermodilution (L/min/m2) Right atrial pressure (mmHg)

Full Information

First Posted
July 3, 2015
Last Updated
January 28, 2019
Sponsor
Centre Hospitalier Universitaire de Nice
Collaborators
Assistance Publique Hopitaux De Marseille, University Hospital, Toulouse, University Hospital, Grenoble, Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT02525926
Brief Title
Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension
Acronym
DENERV'AP
Official Title
Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
Refusal of CPP to extend the period of inclusion
Study Start Date
January 2016 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice
Collaborators
Assistance Publique Hopitaux De Marseille, University Hospital, Toulouse, University Hospital, Grenoble, Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
denervation
Arm Type
Experimental
Arm Title
control group
Arm Type
Sham Comparator
Intervention Type
Procedure
Intervention Name(s)
denervation
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
sham procedure
Intervention Description
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 Measure Information:
Title
Mean pulmonary artery pressure (in mmHg) measured during right heart catheterization
Time Frame
at 6 month
Secondary Outcome Measure Information:
Title
Mean pulmonary artery pressure (in mmHg) from the initial procedure
Time Frame
at 3 month
Title
Pulmonary vascular resistance (in Wood units) measured during right cardiac catheterization.
Time Frame
at 6 month
Title
Clinical parameters: NYHA class
Time Frame
at 6 month
Title
Clinical parameters: Borg dyspnea rating scale
Time Frame
at 6 month
Title
Clinical parameters: 6-minute walk test (distance walked in meters),
Time Frame
at 6 month
Title
Clinical parameters: oxygen dependence (quantity of oxygen in L/min),
Time Frame
at 6 month
Title
Clinical parameters: ECG with supra ventricular arrhythmia.
Time Frame
at 6 month
Title
Biological parameters: levels of Brain Natriuretic Peptide (pg/ml) in non-fasting morning samples.
Time Frame
at 6 month
Title
Biological parameters: levels of troponin Ic (ng/ml) in non-fasting morning samples.
Time Frame
at 6 month
Title
Echocardiographic parameters of right ventricular function
Description
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
Time Frame
at 6 month
Title
Other hemodynamic parameters obtained by right cardiac catheterization
Description
Cardiac index/output using thermodilution (L/min/m2) Right atrial pressure (mmHg)
Time Frame
at 6 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
CHU de Grenoble
City
Grenoble
ZIP/Postal Code
38700
Country
France
Facility Name
AP-HM
City
Marseille
ZIP/Postal Code
13354
Country
France
Facility Name
CHU de Nice
City
Nice
ZIP/Postal Code
06000
Country
France
Facility Name
CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
AP-HP
City
¨Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

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Pulmonary Artery Denervation for Treatment of Pulmonary Arterial Hypertension

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