APART-AF: Effect of ARNI in Patients With Persistent AF and Enlarged Left Atrium After Catheter Ablation

Sponsor

The Second Affiliated Hospital of Chongqing Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03791723

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this clinical randomized trial is to evaluate the efficacy and safety of Sacubitril/Valsartan compared with ARB in improving cardiac remodeling in patients With Enlarged Left Atrium Diameter and Persistent AF.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Cardiac Remodeling, Atrial Sacubitril/Valsartan	Drug: Sacubitril-Valsartan Drug: Valsartan	N/A

Detailed Description

Atrial fibrillation is one of the most common arrhythmia around the word. Prolonged atrial fibrillation may lead to structural changes in the heart such as atrial enlargement, which is an important risk factor for heart failure. Sacubitril/Valsartan is a new drug for the treatment of heart failure, previous studies have shown that it has a good effect in improving cardiac function. For patients with persistent atrial fibrillation and enlarged left atrial, the effect of reversing cardiac remodeling after catheter ablation is unclear. Some studies have described its positive effects in improving cardiac remodeling, but there is still no large-scale randomized controlled trial to further confirm. The investigators hypothesized that Sacubitril/Valsartan can reverse cardiac remodeling in patients with persistent atrial fibrillation and enlarged left atrium compared with ARB after catheter ablation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

two groups,group one is for Sacubitril/valsartan 200mg bid or tolerable maximum dose, group two is for valsartan 80mg qd or tolerable maximum dose.two groups,group one is for Sacubitril/valsartan 200mg bid or tolerable maximum dose, group two is for valsartan 80mg qd or tolerable maximum dose.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of ARNI in Reversing Cardiac Remodeling After Catheter Ablation for Patient With Persistent Atrial Fibrillation and Enlarged Left Atrial

Anticipated Study Start Date :

Jun 1, 2019

Anticipated Primary Completion Date :

Jan 1, 2021

Anticipated Study Completion Date :

Dec 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sacubitril/valsartan After catheter ablation, during a single blind, run-in period, participants received placebo. Then started with 50 mg sacubitril/valsarta for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.	Drug: Sacubitril-Valsartan After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 50 mg LCZ696 for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.
Active Comparator: Valsartan After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40mg Valsartan twice daily qd for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.	Drug: Valsartan After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40 mg Valsartan daily (qd) for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.

Arm

Intervention/Treatment

Experimental: Sacubitril/valsartan

After catheter ablation, during a single blind, run-in period, participants received placebo. Then started with 50 mg sacubitril/valsarta for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.

Drug: Sacubitril-Valsartan

After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 50 mg LCZ696 for 2-4 weeks, then uptitrated to 100 mg bid for 2-4 weeks, and thereafter, uptitrated to 200 mg bid or tolerable maximum dose ≥6 months.

Active Comparator: Valsartan

After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40mg Valsartan twice daily qd for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.

Drug: Valsartan

After catheter ablation,during a single blind, run-in period, participants received placebo. Then started with 40 mg Valsartan daily (qd) for 2-4 weeks, then were uptitrated to 80mg qd or tolerable maximum dose ≥6 months.

Outcome Measures

Primary Outcome Measures

Left atrial size changes compared to baseline levels [6months and 12 months]
Echocardiography was used to assess the size of the left atrium, and the changes in atrial structure and baseline levels were compared. The effective index was a gradual decrease in the atrium.

Secondary Outcome Measures

Freedom from AF or AT without the use of antiarrhythmic drugs at 12 months after a single ablation procedure. [12 months]
Confirmation of atrial fibrillation by electrocardiogram or dynamic electrocardiogram during follow-up. Patients with AF or AT that occurred in the first 3 months after the ablation (blanking period) were censored. Each episode that lasted >30 s was regarded as a recurrence.
all-cause death [12 months]
all-cause death
Time to first documented recurrence of atrial arrhythmias [12 months]
Time to first documented recurrence of atrial arrhythmias
Number of hospitalizations caused by heart failure [12 months]
Number of hospitalizations caused by heart failure
All-cause hospitalizations [12 months]
All-cause hospitalizations
Number of patients requires adjustment of the drug because of Hypotension [12 months]
Number of patients requires adjustment of the drug because of Hypotension
Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction [12 months]
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.
Right atrial size changes compared to baseline levels [12 months]
Echocardiography was used to assess the size of the right atrium, and the changes in atrial structure and baseline levels were compared. The effective index was a gradual decrease in the atrium.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with persistent atrial fibrillation undergoing catheter ablation within 2 weeks.
≥18 and ≤75 years of age.
Left atrium diameter（LAD）≥35mm, With or without right atrium diameter（RAD）≥40mm，diagnosed by Echocardiographic.
patient who are mentally and linguistically able to understand the aim of the trial and to show sufficient compliance in following the trial protocol.
Patients receiving ACE inhibitors (ACEI), angiotensin receptor blockers (ARB) and/or a beta blockers must be on a stable dose of these medications stable for the 1 month period prior to Visit.
Patients with a controlled systolic BP, defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mmHg are eligible for enrollment if they are on three or more medications to control BP at randomization.
Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the Modification of Diet in Renal Disease formula).
Patients with a potassium ≤5.2 mmol/l at Visit 1.

Exclusion Criteria:

Patients with prosthetic valves.
Any previous LA suigery.
Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention within 3 months or and elective PCI within 30 days prior to entry.
Presence of hemodynamically significant mitral and /or aortic valve disease.
Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
Current acute decompensated HF requiring therapy.
Allergic to drugs or active ingredients (shakuba, valsartan) or any excipients。
Patients with previous history of angioedema associated with ACEI or ARB treatment.
Patient with hereditary or idiopathic angioedema.
patient with severe liver damage, biliary cirrhosis and cholestasis.
Patient with Renal artery stenosis.