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

NCT ID: NCT03791723

Last Updated: 2019-03-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-01
• Study Completion Date: 2021-12-30

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.

Conditions

Atrial Fibrillation; Cardiac Remodeling, Atrial; Sacubitril/Valsartan

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sacubitril-Valsartan

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Valsartan

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Second Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Yuehui Yin

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

ZHIYU LING, MD

Role: CONTACT

lingzy1977@163.com

+8613512362075

YANPING XU

Role: CONTACT

+86-023-63693079

References

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.

Reference Type: BACKGROUND

PMID: 29348971 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29754651 (View on PubMed)

Other Identifiers

APART-AF

Identifier Type: -

Identifier Source: org_study_id