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

NCT02284737 | Terminated Phase 4 DMC

• 1 other identifier: FirstNanjingMU
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary arterial hypertension

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to month 6

Secondary Outcomes (11)

• 6-minute walk distance

  Baseline to month 6

• Pulmonary arterial pressure

  Baseline to month 6

• Right atrial pressure

  Baseline to month 6

• Pulmonary Vascular Resistance

  Baseline to month 6

• Cardiac output

  Baseline to month 6

Other Outcomes (3)

• Pulmonary artery perforation

  During PADN procedure

• Pulmonary embolism

  6 months

• The prognostic role of 18F-DOPA PET/CT in patients with PAH

  6 months

Study Arms (2)

PADN + sildenafil

EXPERIMENTAL

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.

Procedure: PADN; Drug: Sildenafil

sham PADN + sildenafil

SHAM COMPARATOR

The radiofrequency ablation catheter placed, no ablations.

Procedure: sham PADN; Drug: Sildenafil

Interventions

PADN PROCEDURE

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.

Also known as: Pulmonary artery denervation

PADN + sildenafil

sham PADN PROCEDURE

The radiofrequency ablation catheter placed, no ablations for patients in the sham PADN group.

Also known as: sham pulmonary artery denervation

sham PADN + sildenafil

Sildenafil DRUG

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.

Also known as: Viagra

PADN + sildenafil; sham PADN + sildenafil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Nanjing First Hospital, Nanjing Medical University: lead

Study Sites (1)

Nanjing First Hospital

Nanjing, Jiangsu, 210006, China

Location

Related Publications (2)

• 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.

  PMID: 23850902 BACKGROUND

• 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.

  PMID: 23466961 BACKGROUND

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Shao-Liang Chen, MD

  Nanjing First Hospital, Nanjing Medical University, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: November 6, 2014
• Study Start: November 28, 2014
• Primary Completion: July 30, 2021
• Study Completion: July 30, 2021
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)