Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effective Study of ARNI on Ventricular Arrhythmia in HFrEF Patients With ICD or CRT-D

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04491136
Recruitment Status : Recruiting
First Posted : July 29, 2020
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to generate effectiveness data of ARNI, in the Chinese HFrEF patients with implanted ICD or CRT-D. This will be a multicenter, interventional, open-label, and prospective single-arm study to evaluate the effect of ARNI on VAs in approximately 275 HFrEF patients receiving ICD or CRT-D in China.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: ACEI/ARB Drug: ARNI Phase 4

Detailed Description:

The rationale of this study is to compare the effect of ACEI/ARB with the effect of ARNI on VA events for HFrEF patients with ICD or CRT-D, thus a multicenter, interventional, open-label, and prospective single-arm study was considered.

Study design:This will be a multicenter, interventional, open-label, and prospective single-arm study to evaluate the effect of ARNI on VAs in approximately 275 HFrEF patients receiving ICD or CRT-D in China.

After the patient is informed and asked to sign an informed consent form, baseline data will be collected. Device data of patients will be collected for 12 months. ACEI/ARB will be given to the patient for 6 months. Dosage of ACEI/ARB will be based on investigator's discretion and up titrated after 2-4 weeks to the maximum dosage the patients can tolerate and according to product label.After 6 months, patients using ACEI need to undergo a 36-hr washout period (36-hr washout period is not needed for patients using ARB at month 6). Patients will then receive ARNI (sponsored by Novartis only for this study) while the dosage of ARNI will be according to investigator's discretion and up titrated to the maximum dosage the patient can tolerate or 200 mg bid as per guideline.All patients will be followed up for 6 months for each treatment. After patients finalize the trial, the investigator will evaluate all patients and produce a report.

Primary objective of this study is to assess the proportion of patients with VA events over 6 months of ACEI/ARB and 6 months of ARNI treatment.

Secondary Objectives include:To assess numbers of occurrences of VA events and ICD or CRT-D shocks over 6 months of ACEI/ARB and 6 months of ARNI treatment; To compare the changes in LVEF and NYHA level between ACEI/ARB and ARNI treatment; To compare the changes in the NT-proBNP level between ACEI/ARB and ARNI treatments; To compare the healthcare resource utilization of HF patients during ACEI/ARB and ARNI treatments;

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 275 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Interventional, Open-label and Single-arm Study to Investigate the Effect of ARNI on Ventricular Arrhythmia in HFrEF Patients With ICD or CRT-D
Actual Study Start Date : November 11, 2020
Estimated Primary Completion Date : August 30, 2022
Estimated Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arrhythmia

Arm Intervention/treatment
Experimental: ACEI/ARB treatment in 6 months/ARNI treatment in next 6 months

Angiotensin-converting enzyme inhibitor/Angiotensin receptor blockers treatment in the first 6 months

Angiotensin receptor neprilysin inhibitor treatment in next 6 months

Drug: ACEI/ARB
initative ACE/ARB drug for 6 months in this study

Drug: ARNI
initative ARNI drug for next 6 months in this study




Primary Outcome Measures :
  1. Proportion of patients with VA, ICD and ATP events over 6 months of ACEI/ARB and 6 months of ARNI treatment [ Time Frame: 12 months ]

    Paired proportion of patients by occurrence of at least one Ventricular arrhythmia (VA), Implantable cardioverter defibrillator (ICD ) & Antitachycardia pacing (ATP) event over 6 months of Angiotensin-converting enzyme inhibitor/Angiotensin receptor blockers(ACEI/ARB) & Angiotensin receptor neprilysin inhibitor (ARNI) treatment respectively. VA events defined as: NSVT(Non-sustained ventricular tachycardia), SVT(Sustained ventricular tachycardia),PVC(Premature ventricular contraction), SVT is defined as: tachycardia with haemodynamic disorder or lasting for ≥30 seconds. NSVT is defined as: different ICD devices. PVC is defined as: early ventricular depolarization as determined by device.

    ICD events: Ventricular tachycardia occurrence in implantable cardioverter defibrillator (ICD) patients may result in shock delivery & is associated with increased morbidity & mortality.

    ATP events: Anti-tachycardia pacing is defined as a low-energy alternative to high-energy biphasic shocks.



Secondary Outcome Measures :
  1. Numbers of NSVT, SVT, PVC, ICD shock and ATP experienced by patients [ Time Frame: baseline, 12 month ]
    To assess the number of occurrences of Ventricular arrhythmia (VA) events and Implantable cardioverter defibrillator (ICD) or Cardiac resynchronization therapy-defibrillator (CRT-D) shocks over 6 months of ACEI/ARB and 6 months of ARNI treatment

  2. LVEF (%) [ Time Frame: baseline ,12 month ]
    To compare the changes in Left Ventricular Ejection Fraction (LVEF) and New York Heart Association (NYHA) level between ACEI/ARB and ARNI treatments

  3. NT-proBNP (pg/mL) level [ Time Frame: baseline, 12 month ]
    To compare the changes in the N-Terminal prohormone of Brain Natriuretic Peptide(NT-proBNP) level between ACEI/ARB and ARNI treatments

  4. Number of hospitalizations for arrhythmia or HF related hospitalizations [ Time Frame: baseline, 12 month ]
    To compare the healthcare resource utilization of Heart Failure (HF) patients during ACEI/ARB and ARNI treatments



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion criteria:

  1. Male or female patients ≥18 and ≤80 years of age
  2. Implanted with an ICD or CRT-D within 2 weeks
  3. NYHA functional class II - IV
  4. LVEF ≤40% (measured by echocardiography)
  5. Signed informed consent must be obtained prior to participation in the study.

Key Exclusion criteria

  1. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
  2. Patients who received ARNI within 6 weeks prior to study enrollment
  3. Participation in other clinical studies 3 months prior to participating study
  4. Advanced cancer or other significant comorbidities with life expectancy of <1 year
  5. Previous history of angioedema associated with ACEI/ARB treatment, hereditary or idiopathic angioedema
  6. Patients with renal artery stenosis history
  7. Current stage D HF patients requiring vasoactive drugs
  8. Symptomatic hypotension < 100/60 mmHg at Visit 1 (screening) or Symptomatic hypotension < 90/60 mmHg in anti-hypertension drug treatment at Visit 1 (screening)
  9. Serum potassium >5.4 mmol/L at Visit 1 (screening)
  10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 as measured at Visit 1 (screening)
  11. Pregnant or nursing (lactating) women
  12. Other exclusion depend on investigator's discretion

Other protocol- defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04491136


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
Layout table for location information
China, An Hui
Novartis Investigative Site Recruiting
Hefei, An Hui, China, 230001
China, Henan
Novartis Investigative Site Recruiting
Zhengzhou, Henan, China, 450000
China, Hunan
Novartis Investigative Site Recruiting
Changsha, Hunan, China, 410011
China, Jiangsu
Novartis Investigative Site Recruiting
Nanjing, Jiangsu, China
Novartis Investigative Site Recruiting
Nantong, Jiangsu, China, 226000
Novartis Investigative Site Recruiting
Wu XI, Jiangsu, China, 214023
Novartis Investigative Site Recruiting
Xuzhou, Jiangsu, China, 221000
China, Liaoning
Novartis Investigative Site Recruiting
Dalian, Liaoning, China, 116011
Novartis Investigative Site Recruiting
Shenyang, Liaoning, China, 110011
China, Shandong
Novartis Investigative Site Recruiting
Qingdao, Shandong, China, 266003
China, Shanghai
Novartis Investigative Site Recruiting
Shanghai, Shanghai, China, 200433
China, Shanxi
Novartis Investigative Site Recruiting
Xian, Shanxi, China, 710061
China, Sichuan
Novartis Investigative Site Recruiting
Chengdu, Sichuan, China, 610031
Novartis Investigative Site Recruiting
Chengdu, Sichuan, China, 610041
China, Zhejiang
Novartis Investigative Site Recruiting
Hangzhou, Zhejiang, China, 310014
China
Novartis Investigative Site Recruiting
Guangzhou, China, 510000
Novartis Investigative Site Recruiting
Tianjin, China, 300000
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04491136    
Other Study ID Numbers: CLCZ696BCN04
First Posted: July 29, 2020    Key Record Dates
Last Update Posted: March 26, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LCZ696
sacubitril/valsartan
Heart Failure
Heart failure with reduced ejection fraction
HFrEF
Ventricular arrhythmias
Implanted Device
Healthcare resource utilization
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes