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

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

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.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation; Cardiac Remodeling, Atrial; Sacubitril/Valsartan
• Intervention / Treatment: Drug: Sacubitril-Valsartan; Drug: Valsartan

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 Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: YANPING XU; Phone Number: +86-023-63693079

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left atrial size changes compared to baseline levels	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.	6months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from AF or AT without the use of antiarrhythmic drugs at 12 months after a single ablation procedure.	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.	12 months
all-cause death	all-cause death	12 months
Time to first documented recurrence of atrial arrhythmias	Time to first documented recurrence of atrial arrhythmias	12 months
Number of hospitalizations caused by heart failure	Number of hospitalizations caused by heart failure	12 months
All-cause hospitalizations	All-cause hospitalizations	12 months
Number of patients requires adjustment of the drug because of Hypotension	Number of patients requires adjustment of the drug because of Hypotension	12 months
Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction	A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.	12 months
Right atrial size changes compared to baseline levels	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.	12 months

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Publications and helpful links

General Publications

• Januzzi JL, Butler J, Fombu E, Maisel A, McCague K, Pina IL, Prescott MF, Riebman JB, Solomon S. Rationale and methods of the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF). Am Heart J. 2018 May;199:130-136. doi: 10.1016/j.ahj.2017.12.021. Epub 2018 Feb 13.
• Almufleh A, Marbach J, Chih S, Stadnick E, Davies R, Liu P, Mielniczuk L. Ejection fraction improvement and reverse remodeling achieved with Sacubitril/Valsartan in heart failure with reduced ejection fraction patients. Am J Cardiovasc Dis. 2017 Dec 20;7(6):108-113. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: December 31, 2018
• First Submitted That Met QC Criteria: December 31, 2018
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Sacubitril/Valsartan; Cardiac Remodeling
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Remodeling; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: APART-AF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No