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A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH (PADN-PAH)

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
PADN
sham PADN
Sildenafil
Sponsored by
Nanjing First Hospital, Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary arterial hypertension

Eligibility Criteria

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

Inclusion Criteria:

  • Provision of informed consent prior to any study specific procedures;
  • Men and women 18 years and older;
  • Group I PAH, defined as a mPAP≥25mmHg, PCWP<15mmHg and PVR[The PVR =(mPAP-PCWP)/CO]>3.0 Woods unit.

Exclusion Criteria:

General exclusion criteria:

  • Pregnancy and breast feeding mother;
  • Estimated life expectancy <12 months;
  • Scheduled major surgery in the next 6 months;
  • Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk;
  • Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 30 days.

Procedural exclusion criteria:

  • WHO group II, III, IV, V PH
  • Severe Renal dysfunction (Ccr<30 ml/min)
  • Blood platelet count<100,000/L
  • Expected life span<6-month
  • Systematical inflammation
  • Malignant cancer(s)
  • Tricuspid valve stenosis, Supra-pulmonary valve stenosis
  • Allergic to studied drugs or metal materials.

Sites / Locations

  • Nanjing First Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

PADN + sildenafil

sham PADN + sildenafil

Arm Description

Two to three ablations at 1-15 W for 120 seconds at each point were performed in the distal bifurcation area of the main PA.

The radiofrequency ablation catheter placed, no ablations.

Outcomes

Primary Outcome Measures

Pulmonary artery hypertension (PAH)- related events
Including all-cause death, lung transplantation, atrial septostomy, worsening of PAH, initiation of treatment with intravenous or subcutaneous prostacyclin

Secondary Outcome Measures

6-minute walk distance
The 6-minute walk distance (6MWD) test was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.).
Pulmonary arterial pressure
Pulmonary arterial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration.
Right atrial pressure
Right atrial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration.
Pulmonary Vascular Resistance
PVR=[mean pulmonary arterial pressure-pulmonary artery occlusion pressure] / cardiac output
Cardiac output
The amount of blood the heart pumps through the circulatory system in a minute. Measured by right heart catheterization.
Trans-pulmonary pressure gradient
The transpulmonary pressure gradient (TPG), defined by the difference between mean pulmonary arterial pressure (P(pa)) and left atrial pressure (P(la).
Diastolic pressure gradient
The diastolic pressure gradient (DPG), defined by the difference between mean pulmonary arterial pressure and PA occlusion pressure.
Pulmonary arterial compliance
Pulmonary arterial compliance was obtained with a 7-F flow-directed Swan-Ganz catheter.
Borg Dyspnea Index
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
World Health Organization (WHO) Functional Class
WHO Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possible at rest.
New York functional class
NYHA Classes: I) Patients with no limitation of activities; they suffer no symptoms from ordinary activities. II) Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion. III) Patients with marked limitation of activity; they are comfortable at rest. IV) Patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.

Full Information

First Posted
October 28, 2014
Last Updated
August 18, 2021
Sponsor
Nanjing First Hospital, Nanjing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT02284737
Brief Title
A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
Acronym
PADN-PAH
Official Title
A Prospective, Multi-center, Randomized Control Trial to Investigate the Efficacy of Pulmonary Artery Denervation to Improved Functional Capacity and Hemodynamics in Patients With Pulmonary Artery Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Lack of subjects.
Study Start Date
November 28, 2014 (Actual)
Primary Completion Date
July 30, 2021 (Actual)
Study Completion Date
July 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nanjing First Hospital, Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Pulmonary arterial hypertension (PAH) is characterized by premature death mainly because of progressive and severe right ventricular failure. Target drugs are reported to be associated with significant improvement of clinical outcome for PAH patients. However, previous studies using those target drugs focused on the change of 6-minute walk distance (6MWD) and or hemodynamic responses. As 6MWD has weak correlation with clinical outcome (time to clinical worsening, TTCW), benefits from target drugs for PAH patients are not clear. We previously reported the safety and efficacy of pulmonary artery denervation (PADN) for treatment of PAH patients who were unresponsive to target drugs. Hence, we design the randomized study to identify the effect of PADN on PAH.
Detailed Description
The current study is designed as a multicenter, randomized and prospective study aiming to compare the effect of PADN on PAH patients. Based on the previous studies, the rate of pulmonary arterial hypertension (PAH)-related event was around 30% after 6-month treatment using target drugs. And our previous data showed that this PAH-related event at 6-month after PADN procedure was 15%. As a result, a total of 270 PAH patients was required, with 135 patients/per group at a ratio of 1:1 randomization. All patients underwent an 18F-DOPA PET/CT scan of pulmonary arteries and the heart, performed at basement.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PADN + sildenafil
Arm Type
Experimental
Arm Description
Two to three ablations at 1-15 W for 120 seconds at each point were performed in the distal bifurcation area of the main PA.
Arm Title
sham PADN + sildenafil
Arm Type
Sham Comparator
Arm Description
The radiofrequency ablation catheter placed, no ablations.
Intervention Type
Procedure
Intervention Name(s)
PADN
Other Intervention Name(s)
Pulmonary artery denervation
Intervention Description
Contrast pulmonary artery angiography is performed to localize the pulmonary artery bifurcation level and to calculate the PA diameter. Once the anatomy is deemed acceptable, the radiofrequency ablation catheter is introduced into the distal bifurcation area of the main PA. The catheter is then maneuvered within the PA to allow energy delivery to ensure that the electrodes are tightly in contact with the endovascular surface. Two to three ablations at 1-15 W for 120 seconds at each point were performed in the distal bifurcation area of the main PA.
Intervention Type
Procedure
Intervention Name(s)
sham PADN
Other Intervention Name(s)
sham pulmonary artery denervation
Intervention Description
The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Other Intervention Name(s)
Viagra
Intervention Description
Participants initially received 5 mg tadalafil for the first 2 weeks in the two groups. The tadalafil dose may have been up titrated to 40 mg after 2 weeks, with maximum effects being obtained. The up titrated of tadalafil to 40 mg was not mandatory if the investigator decided for tolerability reasons the participants should remain on 5 mg.
Primary Outcome Measure Information:
Title
Pulmonary artery hypertension (PAH)- related events
Description
Including all-cause death, lung transplantation, atrial septostomy, worsening of PAH, initiation of treatment with intravenous or subcutaneous prostacyclin
Time Frame
Baseline to month 6
Secondary Outcome Measure Information:
Title
6-minute walk distance
Description
The 6-minute walk distance (6MWD) test was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.).
Time Frame
Baseline to month 6
Title
Pulmonary arterial pressure
Description
Pulmonary arterial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration.
Time Frame
Baseline to month 6
Title
Right atrial pressure
Description
Right atrial pressure was obtained with a 7-F flow-directed Swan-Ganz catheter at end-expiration.
Time Frame
Baseline to month 6
Title
Pulmonary Vascular Resistance
Description
PVR=[mean pulmonary arterial pressure-pulmonary artery occlusion pressure] / cardiac output
Time Frame
Baseline to month 6
Title
Cardiac output
Description
The amount of blood the heart pumps through the circulatory system in a minute. Measured by right heart catheterization.
Time Frame
Baseline to month 6
Title
Trans-pulmonary pressure gradient
Description
The transpulmonary pressure gradient (TPG), defined by the difference between mean pulmonary arterial pressure (P(pa)) and left atrial pressure (P(la).
Time Frame
Baseline to month 6
Title
Diastolic pressure gradient
Description
The diastolic pressure gradient (DPG), defined by the difference between mean pulmonary arterial pressure and PA occlusion pressure.
Time Frame
Baseline to month 6
Title
Pulmonary arterial compliance
Description
Pulmonary arterial compliance was obtained with a 7-F flow-directed Swan-Ganz catheter.
Time Frame
Baseline to month 6
Title
Borg Dyspnea Index
Description
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Time Frame
Baseline to month 6
Title
World Health Organization (WHO) Functional Class
Description
WHO Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possible at rest.
Time Frame
Baseline to month 6
Title
New York functional class
Description
NYHA Classes: I) Patients with no limitation of activities; they suffer no symptoms from ordinary activities. II) Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion. III) Patients with marked limitation of activity; they are comfortable at rest. IV) Patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.
Time Frame
Baseline to month 6
Other Pre-specified Outcome Measures:
Title
Pulmonary artery perforation
Description
Number of Participants with pulmonary artery perforation
Time Frame
During PADN procedure
Title
Pulmonary embolism
Description
PE is classified by suspected and fatal ones. Suspected PE is defined as one of the following: 1) new intra-luminal filling defect on CT scan, MRI scan, or pulmonary angiogram; 2)new perfusion defect of at least 75% on V/Q lung scan; and 3) inconclusive spiral CT, pulmonary angiography or lung scan with demonstration of deep vein thrombosis in the lower extremities by venography. Fatal PE is PE based on objective diagnostic testing or autopsy or death not attributed to a documented cause and for which deep vein thrombosis/PE cannot be ruled out.
Time Frame
6 months
Title
The prognostic role of 18F-DOPA PET/CT in patients with PAH
Description
the prognostic role of 18F-DOPA PET/CT in patients with PAH.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of informed consent prior to any study specific procedures; Men and women 18 years and older; Group I PAH, defined as a mPAP≥25mmHg, PCWP<15mmHg and PVR[The PVR =(mPAP-PCWP)/CO]>3.0 Woods unit. Exclusion Criteria: General exclusion criteria: Pregnancy and breast feeding mother; Estimated life expectancy <12 months; Scheduled major surgery in the next 6 months; Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk; Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 30 days. Procedural exclusion criteria: WHO group II, III, IV, V PH Severe Renal dysfunction (Ccr<30 ml/min) Blood platelet count<100,000/L Expected life span<6-month Systematical inflammation Malignant cancer(s) Tricuspid valve stenosis, Supra-pulmonary valve stenosis Allergic to studied drugs or metal materials.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shao-Liang Chen, MD
Organizational Affiliation
Nanjing First Hospital, Nanjing Medical University, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nanjing First Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210006
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23850902
Citation
Chen SL, Zhang FF, Xu J, Xie DJ, Zhou L, Nguyen T, Stone GW. Pulmonary artery denervation to treat pulmonary arterial hypertension: the single-center, prospective, first-in-man PADN-1 study (first-in-man pulmonary artery denervation for treatment of pulmonary artery hypertension). J Am Coll Cardiol. 2013 Sep 17;62(12):1092-1100. doi: 10.1016/j.jacc.2013.05.075. Epub 2013 Jul 10.
Results Reference
background
PubMed Identifier
23466961
Citation
Chen SL, Zhang YJ, Zhou L, Xie DJ, Zhang FF, Jia HB, Wong SS, Kwan TW. Percutaneous pulmonary artery denervation completely abolishes experimental pulmonary arterial hypertension in vivo. EuroIntervention. 2013 Jun 22;9(2):269-76. doi: 10.4244/EIJV9I2A43.
Results Reference
background

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A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH

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