A Trial to Evaluate the Safety and Efficacy of Pulmonary Artery Denervation for the Treatment of Pulmonary Hypertension Associated With Left Heart Failure

NCT ID: NCT05824923

Last Updated: 2024-09-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

264 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-14

Study Completion Date

2027-02-28

Brief Summary

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It's a phase III, prospective, multicenter, randomized controlled trial to evaluate the safety and efficacy of the pulmonary artery denervation (PADN) for heart failure (HF) patients diagnosed with pulmonary hypertension associate with left heart disease (PH-LHD) by right heart catheterization.

Detailed Description

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Chronic heart failure (CHF) patients who have received guideline-directed medical therapy (GDMT) based on the 2023 ESC Guidelines for HF and have reached clinical stable, and diagnosed with PH-LHD by right heart catheterization, will be randomized to the PADN group or control group in a 1:1 ratio to receive PADN combined with HF GDMT or HF GDMT, respectively. After the 12-month follow-up visit is completed, participants in the control group who still meet the inclusion and exclusion criteria can also choose to receive PADN.

Approximately 264 participants will be enrolled at up to 39 centers in China and followed for 3 years. The safety and efficacy of the PADN system, including RF ablation catheter and generator will be evaluated by comparing the therapeutic effect of the PADN group and the control group.

Conditions

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Pulmonary Hypertension Heart Failure With Reduced Ejection Fraction Hypertension Vascular Diseases Cardiovascular Diseases Heart Failure Heart Failure With Preserved Ejection Fraction Heart Failure With Mid Range Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

At the 12-months visit, participants in the control group who still meet the inclusion and exclusion criteria can choose to receive PADN procedure.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Pulmonary Artery Denervation (PADN)

Patients in the PADN group will receive pulmonary artery denervation procedure.

Group Type EXPERIMENTAL

Pulmonary arterial denervation

Intervention Type PROCEDURE

Contrast pulmonary artery (PA) angiography will be performed to localize the pulmonary artery bifurcation level and calculate the PA diameter. Once the anatomy deemed acceptable, the radiofrequency ablation catheter will be introduced into ostium of the left PA and the distal bifurcation area of the main PA.

The catheter will be manoeuvred within the PA to allow energy delivery in a circumferential manner to ensure that the electrodes are tightly in contact with the endovascular surface. About three ablations at 45-55 ℃ for 120 seconds each will be performed in ostium of the left PA and the distal bifurcation area of the main PA.

For non-atrial fibrillation patients, dual antiplatelet therapy for 1 month after PADN is recommended. Patients with atrial fibrillation should continue new oral anticoagulants and patients who underwent metal valve replacement should continued oral warfarin anticoagulation according to guidelines, which could determined by the physician.

Guideline-directed medical therapy (GDMT) for heart failure

Intervention Type DRUG

GDMT medication recommendation including:

* Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI)
* Beta-receptor blocker (BB)
* Mineralocorticoid receptor antagonist (MRA)
* Sodium-glucose co-transporter 2 (SGLT2) inhibitor
* Diuretics

The medication regimen (type and dosage) will be the investigator's discretion in accordance with the 2023 ESC Guidelines for Heart Failure. The type and dosage of all GDMT medications (except for diuretics) should remain unchanged through follow-up duration (at 12-month visit), unless the participant's conditions need adjust of GDMT regimens. Dosage and single or combination of diuretics are all left at physician's discretion.

Guideline-directed medical therapy (GDMT) for heart failure

Patients in the control group will take their baseline anti-heart failure medications at the original doses according to 2023 ESC Guidelines for heart failure, without any changes except when medically required. The anti-heart failure drugs treatment is consistent in both arms.

Group Type ACTIVE_COMPARATOR

Guideline-directed medical therapy (GDMT) for heart failure

Intervention Type DRUG

GDMT medication recommendation including:

* Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI)
* Beta-receptor blocker (BB)
* Mineralocorticoid receptor antagonist (MRA)
* Sodium-glucose co-transporter 2 (SGLT2) inhibitor
* Diuretics

The medication regimen (type and dosage) will be the investigator's discretion in accordance with the 2023 ESC Guidelines for Heart Failure. The type and dosage of all GDMT medications (except for diuretics) should remain unchanged through follow-up duration (at 12-month visit), unless the participant's conditions need adjust of GDMT regimens. Dosage and single or combination of diuretics are all left at physician's discretion.

Interventions

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Pulmonary arterial denervation

Contrast pulmonary artery (PA) angiography will be performed to localize the pulmonary artery bifurcation level and calculate the PA diameter. Once the anatomy deemed acceptable, the radiofrequency ablation catheter will be introduced into ostium of the left PA and the distal bifurcation area of the main PA.

The catheter will be manoeuvred within the PA to allow energy delivery in a circumferential manner to ensure that the electrodes are tightly in contact with the endovascular surface. About three ablations at 45-55 ℃ for 120 seconds each will be performed in ostium of the left PA and the distal bifurcation area of the main PA.

For non-atrial fibrillation patients, dual antiplatelet therapy for 1 month after PADN is recommended. Patients with atrial fibrillation should continue new oral anticoagulants and patients who underwent metal valve replacement should continued oral warfarin anticoagulation according to guidelines, which could determined by the physician.

Intervention Type PROCEDURE

Guideline-directed medical therapy (GDMT) for heart failure

GDMT medication recommendation including:

* Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI)
* Beta-receptor blocker (BB)
* Mineralocorticoid receptor antagonist (MRA)
* Sodium-glucose co-transporter 2 (SGLT2) inhibitor
* Diuretics

The medication regimen (type and dosage) will be the investigator's discretion in accordance with the 2023 ESC Guidelines for Heart Failure. The type and dosage of all GDMT medications (except for diuretics) should remain unchanged through follow-up duration (at 12-month visit), unless the participant's conditions need adjust of GDMT regimens. Dosage and single or combination of diuretics are all left at physician's discretion.

Intervention Type DRUG

Other Intervention Names

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PADN GDMT medication for heart failure

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18, ≤75 years old;
2. Diagnosed with chronic heart failure for at least 3 months, and have received the GDMT pharmacological treatment based on the 2023 ESC Guidelines for Heart Failure for at least 1 month;
3. Clinically stable defined by

1. No intravenous diuretics, inotropes or vasodilators for at least 1 month, and
2. Systolic blood pressure (SBP) ≥ 100 and \< 160 mmHg and resting heart rate (HR) ≥50 and \<100 bpm (\<110 bpm for atrial fibrillation) on the day of the procedure
4. New York Heart Association (NYHA) class II-IVa;
5. 6MWD ≥ 100 m and \< 450 m;
6. NT-proBNP \> 125 pg/mL (BNP \> 35 pg/mL);
7. Hemodynamic indicators (RHC) :

1. Mean pulmonary arterial pressure (mPAP) \> 20 mmHg
2. Pulmonary capillary wedge pressure (PCWP) \>15 mmHg
8. Understand and be willing to sign informed consent, and be willing to follow the follow-up plan required by the protocol.

Exclusion Criteria

1. Any of the following:

1. Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction or systolic anterior motion; pericardial disease; infiltrative or inflammatory myocardial disease; valvular stenosis of any of the 4 valves, or severe regurgitation of aortic and pulmonary valves, or active endocarditis; or
2. Symptomatic carotid stenosis, or transient ischemic attack (TIA) or stroke within 30 days prior to randomization; or
3. Untreated congenital heart disease; or
4. Have received any revascularization, including coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within 6 months prior to randomization; or anticipated to undergo coronary revascularization (CABG or PCI) within 6 months; or
5. Artificial pacemakers, including single-chamber, dual-chamber and three-chamber pacemakers, have been implanted or are anticipated to be implanted within 6 months; or
6. Anticipated to undergo ablation of atrial fibrillation within 6 months; or
7. Anticipated to undergo heart valve surgery (valve replacement, valvuloplasty) within 6 months; or
8. Listing for heart/heart-lung transplantation or anticipated to implant a ventricular assist device (VAD)
2. Other types of pulmonary hypertension, including WHO Group1, Group3, Group4, Group5;
3. Received pulmonary arterial hypertension (PAH) targeted drugs within 1 month prior to randomization;
4. Anticipated to undergo any surgery within 6 months;
5. The cardiac index (CI) of RHC \< 1.5L/min/m²;
6. Severe renal insufficiency (eGFR \<30mL/min/1.73m² by MDRD formula);
7. Severe liver insufficiency (Child-Pugh classification C);
8. Platelet count \< 50 × 10\^9/L;
9. Life expectancy \<1 year;
10. Systemic inflammation or other disease requiring long-term use of glucocorticoids or immunosuppressants;
11. Active infection requiring oral or intravenous antibiotics;
12. Body mass index (BMI) \>40 kg/m²;
13. Pregnant or lactating women, or plan to pregnant in one year;
14. Participated in other clinical trials within 3 months prior to signing the informed consent;
15. Any other circumstances that investigators deem inappropriate to participate in this trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The General Hospital of Northern Theater Command

OTHER

Sponsor Role collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role collaborator

First Hospital of Tsinghua University

OTHER

Sponsor Role collaborator

Cangzhou Central Hospital

OTHER

Sponsor Role collaborator

Chinese Academy of Medical Sciences, Fuwai Hospital

OTHER

Sponsor Role collaborator

Guangdong Provincial People's Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role collaborator

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role collaborator

Tongji Hospital

OTHER

Sponsor Role collaborator

Second Hospital of Jilin University

OTHER

Sponsor Role collaborator

China-Japan Union Hospital, Jilin University

OTHER

Sponsor Role collaborator

Shanxi Cardiovascular Hospital

OTHER

Sponsor Role collaborator

RenJi Hospital

OTHER

Sponsor Role collaborator

Shanghai 10th People's Hospital

OTHER

Sponsor Role collaborator

Beijing Anzhen Hospital

OTHER

Sponsor Role collaborator

West China Hospital

OTHER

Sponsor Role collaborator

Sichuan Academy of Medical Sciences

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role collaborator

TEDA International Cardiovascular Hospital

OTHER

Sponsor Role collaborator

Tianjin Medical University General Hospital

OTHER

Sponsor Role collaborator

Renmin Hospital of Wuhan University

OTHER

Sponsor Role collaborator

Zhongnan Hospital

OTHER

Sponsor Role collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role collaborator

Xiamen Cardiovascular Hospital, Xiamen University

OTHER

Sponsor Role collaborator

Zhejiang University

OTHER

Sponsor Role collaborator

Shengjing Hospital

OTHER

Sponsor Role collaborator

First Affiliated Hospital of Fujian Medical University

OTHER

Sponsor Role collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role collaborator

Gansu Provincial Hospital

OTHER

Sponsor Role collaborator

Yanan Hospital of Kunming City

UNKNOWN

Sponsor Role collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role collaborator

Huaihe Hospital of Henan University

OTHER

Sponsor Role collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role collaborator

Hunan Provincial People's Hospital

OTHER

Sponsor Role collaborator

Tianjin Medical University Second Hospital

OTHER

Sponsor Role collaborator

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role collaborator

The First Hospital of Jilin University

OTHER

Sponsor Role collaborator

Pulnovo Medical (Wuxi) Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yaling Han

Role: PRINCIPAL_INVESTIGATOR

The General Hospital of Northern Theater Command

Locations

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General Hospital of Northern Theater Command

Shenyang, Liaoning, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Mark Gu

Role: CONTACT

13774217349

Yanyan Lu

Role: CONTACT

13914766820

Other Identifiers

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Pulnovo-CO-2022-01

Identifier Type: -

Identifier Source: org_study_id

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