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

NCT ID: NCT02284737

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-28
• Study Completion Date: 2021-07-30

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.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

PADN + sildenafil

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.

Group Type: EXPERIMENTAL

PADN

Intervention Type: 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.

Sildenafil

Intervention Type: 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.

sham PADN + sildenafil

The radiofrequency ablation catheter placed, no ablations.

Group Type: SHAM_COMPARATOR

sham PADN

Intervention Type: PROCEDURE

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

Sildenafil

Intervention Type: 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.

Interventions

PADN

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

sham PADN

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

Intervention Type: PROCEDURE

Sildenafil

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.

Intervention Type: DRUG

Other Intervention Names

Pulmonary artery denervation; sham pulmonary artery denervation; Viagra

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing First Hospital, Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Shaoliang Chen, MD

Vice President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shao-Liang Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Nanjing First Hospital, Nanjing Medical University, China

Locations

Nanjing First Hospital

Nanjing, Jiangsu, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 23850902 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23466961 (View on PubMed)

Other Identifiers

FirstNanjingMU

Identifier Type: -

Identifier Source: org_study_id