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

Not Applicable

• Conditions: Cardiac Remodeling, Atrial; Atrial Fibrillation; Sacubitril/Valsartan
• Interventions: Drug: Sacubitril-Valsartan; Drug: Valsartan

• Registration Number: NCT03791723
• Lead Sponsor: The Second Affiliated Hospital of Chongqing Medical University

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.

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 Timeline

• Study First Submitted: 2018-12-31
• Study First Submitted QC: 2018-12-31
• Study First Posted: 2019-01-03
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-18
• Last Update Posted: 2019-03-19
• Study Start: 2019-06-01
• Primary Completion: 2021-01-01
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Patients with persistent atrial fibrillation undergoing catheter ablation within 2 weeks.
2. ≥18 and ≤75 years of age.
3. Left atrium diameter（LAD）≥35mm, With or without right atrium diameter（RAD）≥40mm，diagnosed by Echocardiographic.
4. patient who are mentally and linguistically able to understand the aim of the trial and to show sufficient compliance in following the trial protocol.
5. 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.
6. 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.
7. Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the Modification of Diet in Renal Disease formula).
8. Patients with a potassium ≤5.2 mmol/l at Visit 1.

Exclusion Criteria

1. Patients with prosthetic valves.
2. Any previous LA suigery.
3. 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.
4. Presence of hemodynamically significant mitral and /or aortic valve disease.
5. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
6. Current acute decompensated HF requiring therapy.
7. Allergic to drugs or active ingredients (shakuba, valsartan) or any excipients。
8. Patients with previous history of angioedema associated with ACEI or ARB treatment.
9. Patient with hereditary or idiopathic angioedema.
10. patient with severe liver damage, biliary cirrhosis and cholestasis.
11. Patient with Renal artery stenosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sacubitril/valsartan	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.
Valsartan	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
all-cause death	12 months	all-cause death
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.
Time to first documented recurrence of atrial arrhythmias	12 months	Time to first documented recurrence of atrial arrhythmias
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.
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