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CTRI Number  CTRI/2014/08/004851 [Registered on: 08/08/2014] Trial Registered Prospectively
Last Modified On: 04/11/2019
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Medical Device 
Study Design  Single Arm Study 
Public Title of Study   A study to determine if therapeutic vagal nerve stimulation could improve functioning of the heart in diastolic heart failure patients. 
Scientific Title of Study   Autonomic Neural Regulation Therapy To Enhance Myocardial Function In Patients With Heart Failure And Preserved Ejection Fraction (Anthem-HFpEF) Study 
Trial Acronym  Anthem-HFpEF 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
C-04, Version 5.0 dated 12 April 2019  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Jayashri Krishnan 
Designation  Deputy Head - Operations  
Affiliation  JSS Medical Research India Private Limited 
Address  No. 13/7, 45th Street, Nanganallur

Chennai
TAMIL NADU
600061
India 
Phone  91-9771407484  
Fax  91-044-43588940  
Email  Jayashri.krishnan@jssresearch.com  
 
Details of Contact Person
Scientific Query
Modification(s)  
Name  Dr Sonika Newar 
Designation  Medical Monitor 
Affiliation  JSS Medical Research India Private Limited 
Address  6th Floor, Vatika Mindscapes (Tower B) Plot 12/2, Sector 27D

Faridabad
HARYANA
121003
India 
Phone  91-8800799887  
Fax  91-129-6613520  
Email  sonika.newar@jssresearch.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Dr Shariq Anwar 
Designation  Head Operations 
Affiliation  JSS Medical Research India Private Limited 
Address  6th Floor, Vatika Mindscapes (Tower B) Plot 12/2, Sector 27D

Faridabad
HARYANA
121003
India 
Phone  91-9810979215  
Fax  91-129-6613520  
Email  shariq.anwar@jssresearch.com  
 
Source of Monetary or Material Support
Modification(s)  
LivaNova, PLC. 100 Cyberonics Blvd. Houston, Texas 77058 USA 
 
Primary Sponsor
Modification(s)  
Name  LivaNova PLC 
Address  100 Cyberonics Blvd. Houston, Texas 77058 USA 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor
Modification(s)  
Name  Address 
JSS Medical Research India Private Limited  6th Floor, Vatika Mindscapes (Tower B) Plot 12/2, Sector 27D Faridabad - 121003, Haryana, India 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 10  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr BK Srinivasa Sastry  CARE Hospital   Exhibition Ground Road, Nampally, Hyderabad-500001, Telangana
Hyderabad
ANDHRA PRADESH 		 91-9849599888

bkssastry@hotmail.com 
Dr Ajay M Naik  Care Institute of Medical Sciences Hospital (CIMS Hospital)  Off science city road, Sola-380060, India
Ahmadabad
GUJARAT 		 91-9825082666

ajay.naik@cimshospital.org 
Dr Aziz Khan  Crescent hospital & Heart Centre  Near Lokmat Square, Dhantoli-440012, India
Nagpur
MAHARASHTRA 		 91-9823056551

kahandraziz@yahoo.com 
Dr Joy M Thomas  Frontier Lifeline Hospital  Ambattur Industrial Estate Road-600001, India
Chennai
TAMIL NADU 		 91-9444406192

joycardio@gmail.com 
Dr Rajendra Kumar Premchand  Krishna Institute of Medical science  Room #46 , 3rd Floor, Block 3, Cardiology department Krishna Institute of Medical science, #1-8-31/1, Minister Road, Secunderabad 500003 Hyderabad (A.P) India
Hyderabad
ANDHRA PRADESH 		 91-9848029443

kumarpre@hotmail.com 
Dr Ulhas M Pandurangi  Madras Medical Mission  Room No. L6, Main Building, Eighth Floor, Madras Medical Mission,4- A, Dr.J.J.Nagar, Mogapair Chennai-600037.
Chennai
TAMIL NADU 		 9841273868
044-6565859
epulhas@gmail.com 
Dr Naresh Trehan  Medanta -The Medicity  Sector - 38, Gurgaon, Haryana- 122001
Gurgaon
HARYANA 		 91-124-4834333

Naresh.Trehan@Medanta.org 
Dr Kamal Sharma  Sanjivani Superspeciality Hospital  1 Uday park Society, Nr. Sun rise Park, Vastrapur, Ahmedabad - 380015
Ahmadabad
GUJARAT 		 91-9426020154

Kamalsharma1975@gmail.com 
Dr Santanu Pradeep Sengupta  Sengupta Hospital and Research Institute  Near Ravinagar square, 440033, India
Nagpur
MAHARASHTRA 		 91-9923190925

senguptasp@gmail.com 
Dr Uday Kumar H  Yashoda Hospital  Room No: 159, OP-V, First Floor, Yashoda Hospital, Behind Harihara Kalabhavan, S. P. Road, Secunderabad-500003, Hyderabad, Telangana, India.
Hyderabad
ANDHRA PRADESH 		 9848039671

uday.hosad@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 10  
Name of Committee  Approval Status 
Care Hospital, Institutional Ethics Committee  Approved 
Crescent Hospital Institutional Ethics Committee  Approved 
Ethics committee of CIMS  Approved 
Institutional Ethics Committee Frontier Lifeline  Approved 
Institutional Ethics Committee, The Madras Medical Mission  Approved 
Institutional Ethics Committee, Yashoda Academy of Medical Education and Research  Approved 
KIMS Intuitional Ethics Committee  Approved 
Medanta Institutional Ethics Committee  Approved 
Sanjivani Hospital Ethics Committee  Approved 
Sengupta Hospital and Research Institute Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: I50||Heart failure,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Implantable VNS therapy system  Patients with symptomatic heart failure will undergo a final follow-up visit prior to study conclusion approximately 6 months after the 12-month follow-up visit is completed for the final enrolled patient. The device being studied includes the Implantable Pulse Generator (Model 103) which is implanted in pectoral region and a VNS Therapy lead (Model 304) which is attached to the cervical vagus nerve. The device is turned on two weeks after implant and the therapy is provided till the device is switched off. The device will provide Intermittent therapeutic vagus nerve stimulation throughout the therapy period  
Comparator Agent  Not applicable.  Not applicable. 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Patients enrolled in the study must meet all of the following criteria:
1. Age 18 years or above
2. Willing and capable of providing informed consent
3. Capable of participating in all the testing associated with this clinical investigation
4. Chronic, symptomatic heart failure NYHA class II/III
5. Stable pharmacologic therapy for at least 1 month
6. On loop diuretic therapy for at least 1 month prior to enrollment
7. Left Ventricular Ejection Fraction (EF) ≥ 40%
8. Plasma NT-proBNP ≥ 220 pg/mL
9. Ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/E’) > 15, or left atrial (LA) enlargement, defined as LA volume index ≥ 29 mL/m2
10. Controlled systolic blood pressure (systolic BP < 140 mmHg, or systolic BP between 140 and 160 mmHg receiving three or more blood pressure medications
11. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 at screening (calculated by the modification of Diet in Renal Disease formula)
12. Physically capable and willing to perform repeated 6-minute walk tests associated with the study, and a baseline distance of between 150 and 425 meters. Symptoms limiting the duration of the 6-minute walk test must be due to heart failure alone
 
 
ExclusionCriteria 
Details  Exclusion Criteria:
Patients who meet any of the following criteria are not eligible to be enrolled in the study:
1. Patients who have been hospitalized for heart failure and who required the use of HF IV therapy in the past 30 days
2. Patients with severe mitral (MR grade 4) or aortic valve disease
3. Patients whose heart failure is due to congenital heart disease
4. Patients with an alternative probable cause for the presenting symptoms, including but not limited to:
a. Isolated right heart failure due to pulmonary disease
b. Dyspnea and/or edema from non-cardiac causes, such as lung disease, anemia, or severe obesity
c. Hemodynamically significant mitral and/or aortic valve disease
d. Hemodynamically significant obstructive lesions of the left ventricular outflow tract, including aortic stenosis
e. Hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis)
5. Patients with a previous documented LVEF < 40%
6. Ratio of mitral velocity to early diastolic velocity of mitral annulus (E/E’) < 8

7. Patients with serum potassium > 5.2 mmol/L
8. Patients with unstable angina, myocardial infarction, PTCA, cerebral vascular accident, or transient ischemic attack in the past 2 months
9. Patients with chronic atrial fibrillation (lasting more than 1 week or requiring cardioversion or pharmacologic conversion) in the past 2 months, or atrial fibrillation with a resting ventricular rate of > 120 bpm
10. Patients with severe pulmonary hypertension
11. Coronary Artery Bypass Surgery (CABG), valve replacement or repair, aortic surgery or PCI) in the past 2 months or anticipated in the next 6 months
12. 1st degree AV block with PR interval > 240 msec, 2nd or 3rd degree AV block
13. Patients with congenital or acquired long QT syndrome
14. Patients unable to tolerate anesthesia required for implant
15. Patients with documented recorded or suspected vasovagal syncope or vasodepressor syncope
16. Patients with a prior vagotomy
17. Patients with prior or existing vagal nerve stimulation treatment
18. Patients with locally implanted semi/permanent devices such as vascular catheters, etc.
19. Patients with cardiac pacemakers, and pacemaker indicated patients
20. Patients who have a cardiac resynchronization therapy (CRT) device, or are scheduled for CRT in the next 6 months
21. Patients who are on an organ transplant list or expected to have an organ transplant within 6 months
22. Patients with a prior cardiac transplant
23. Patients with carotid murmur, vascular bruit, or significant carotid artery disease
24. Patients with known or suspected vascular malformation in the carotid / vertebral circulatory bed
25. Patients who have existing or prior tracheotomy
26. Patients with severe vertebral cervical disease and limited mobility in the neck; includes those that frequently wear a brace
27. Patients who are likely to need an MRI of the neck area because of previous medical conditions
28. Patients with previous neck surgery and resultant scar formation that interferes with the ability to implant the study system
29. Patients actively treated for sleep apnea or sleep disordered breathing with therapies to maintain airway patency with or without oxygen supplementation
30. Patients on or indicated for renal dialysis
31. Patients with diabetes (type I or type II) that is being medically treated for autonomic or sensory neuropathy, or measured hemoglobin A1c (HbA1c) above 8.0% in the past 2 months
32. Patients with hypotension (systolic blood pressure < 80 mmHg)
33. Patient with active peptic ulcer disease or history of upper GI bleeding, or ulcer within 6 months
34. Patients with asthma, history of severe COPD (e.g., FEV1 < 1.5 L), severe restrictive lung disease, or oxygen dependence
35. Patients with known recurrent nerve paralysis
36. Patients with untreated hypothyroidism or hyperthyroidism
37. Patients who have undergone radiotherapy for thyroid disease/cancer
38. Patients who are likely to need shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy
39. Women of childbearing potential who are or might be pregnant at the time of the study or breastfeeding
40. Patients with a life expectancy of less than 12 months per physician judgment
41. Patients involved in any concurrent clinical investigation or have undergone treatment by an investigational drug or device in the past 3 months
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome
Modification(s)  
Outcome  TimePoints 
The primary safety endpoint will be the incidence of procedure and device-related adverse events.   18-48 months 
 
Secondary Outcome
Modification(s)  
Outcome  TimePoints 
• Left atrial volume index
• 6-minute walk
• Quality of Life, using the Minnesota Living with Heart Failure questionnaire
• Physician and Patient Global Assessment
• NYHA Class
• Ratio of diastolic function (E/E’)
• LV mass index
• Heart rate variability (HRV)
• Blood biomarkers(NT-proBNP, creatinine, C-reactive protein)  		 18-48 months 
 
Target Sample Size
Modification(s)  		 Total Sample Size="60"
Sample Size from India="60" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   18/08/2014 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial
Modification(s)  		 Years="5"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  		 A study to see the long- term effect of safety and efficacy of LivaNova VNS Therapy System for the treatment of symptomatic Diastolic heart failure.        
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