| CTRI Number |
CTRI/2019/02/017452 [Registered on: 05/02/2019] Trial Registered Prospectively |
| Last Modified On: |
05/02/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A clinical trial to study the efficacy and safety Ivabradine Extended Release Tablets in comparison to Ivabradine Tablets in patients with stable chronic heart failure with systolic dysfunction in India |
|
Scientific Title of Study
|
A randomized, double blind, double dummy, parallel, multi-centric, comparative study to evaluate efficacy and safety of Ivabradine Extended Release Tablets in comparison to Ivabradine Tablets in patients with stable chronic heart failure with systolic dysfunction in India |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ICR/18/002 Version No. 1.0, Dated 22/AUG/2018 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Nomita Chatterjee Bhandari |
| Designation |
General Manager |
| Affiliation |
Head - India Clinical Research |
| Address |
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai
MAHARASHTRA
400063
India |
| Phone |
02243245397 |
| Fax |
|
| Email |
nomita.bhandari@sunpharma.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Maulik Doshi |
| Designation |
Medical Monitor |
| Affiliation |
Deputy General Manager - India Clinical Research |
| Address |
Sun Pharma laboratories Limited
Tandalja, Vadodara-390020
Gujarat
Vadodara
GUJARAT
390020
India |
| Phone |
02656615500 |
| Fax |
|
| Email |
maulik.doshi@sunpharma.com |
|
Details of Contact Person
Public Query
|
| Name |
Guruprasad Palekar |
| Designation |
Operational Manager |
| Affiliation |
Deputy General Manager - India Clinical Research |
| Address |
Sun Pharma Laboratories Limited
Sun House,
201 B/1, Western Express Highway,
Goregaon ( E),Mumbai 400 063
Mumbai
MAHARASHTRA
400063
India |
| Phone |
02243245215 |
| Fax |
02228947101 |
| Email |
guruprasad.palekar@sunpharma.com |
|
|
Source of Monetary or Material Support
|
| Sun Pharma Laboratories Limited
Sun House,
201 B/1, Western Express Highway,
Goregaon ( E),Mumbai 400 063 |
|
|
Primary Sponsor
|
| Name |
Sun Pharma Laboratories Limited |
| Address |
Sun Pharma Laboratories Limited
Sun House,
201 B/1, Western Express Highway,
Goregaon ( E),Mumbai 400 063 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Behera Kumar Gouraba |
IMS & SUM Hospital |
Department of Cardiology, IMS & SUM Hospital, Siksha OAnusadhan university, Kalinga Nagar, Ghatikia, Bhubaneswar-751003, Odisha
Phone: 917528948833
Email: dr.kumargaurav137@icloud.com
Khordha
ORISSA |
917528948833
dr.kumargaurav137@icloud.com |
| Dr Akhil Sharma |
King Georges Medical University |
Department of Cardiology, King Georges Medical University, Chowk, Lucknow-226003, U.P.
Phone:919198882220
Email: akhil.med@gmail.com
Lucknow
UTTAR PRADESH |
919198882220
akhil.med@gmail.com |
| Dr Sridhar Papani |
Maxcure Hospitals |
Maxcure Hospitals, 1st Floor,
Secretariat Road, Hyderabad-
500063, Telangana State,
India.
Phone: 9490572735.
Email: seedhi139@gmail.com
Hyderabad
TELANGANA |
9490572735
seedhi139@gmail.com |
| Dr Syed Imamuddin |
Osmania Medical College/ Osmania General Hospital |
Osmania Medical College/ Osmania General Hospital, 2nd floor QQDC Building, Department of Cardiology, Afzalgunj, Hyderabad-500012
Phone: 919246885656
Email: drimamheartbeat@gmail.com
Hyderabad
TELANGANA |
919246885656
drimamheartbeat@gmail.com |
| Dr Sinkar Amit Anil |
Oyster & Pearl Hospitals |
Oyster & Pearl Hospitals,
1671-75, Ganeshkhind Road,
Shivajinagar, Pune-411005,
Maharashtra, India.
Phone: 9850704815
Email: dramitsinkar@yahoo.com
Pune
MAHARASHTRA |
9850704815
dramitsinkar@yahoo.com |
| Dr Sohan Kumar Sharma |
SMS Hospital |
Department of Cardiology,
Ground Floor G-2, Dhanvantri
OPD Block SMS Hospital
Jaipur-302004.
Phone: 9680333656.
Email: drsohansharma@gmail.com
Jaipur
RAJASTHAN |
9680333656
drsohansharma@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee, S.M.S Medical College and Attached Hospitals |
Approved |
| IEC IMS and SUM Hospital |
Approved |
| Institutional Ethics Committee, King George’s Medical University |
Submittted/Under Review |
| Institutional Ethics Committee, Max Cure Hospitals |
Approved |
| Institutional Ethics Committee, Osmania Medical college |
Submittted/Under Review |
| O & P Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: I504||Combined systolic (congestive) anddiastolic (congestive) heart failure, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Comparator 1: Ivabradine Tablets 5 mg |
Each patient will be receiving four tablets in a day (two in morning and two in evening). Patient will be
asked to take the medication on regular basis preferably on same time.
Duration: 12 Weeks |
| Comparator Agent |
Comparator 2: Ivabradine Tablets 7.5 mg |
Each patient will be receiving four tablets in a day (two in morning and two in evening). Patient will be asked to take the medication on regular basis preferably on same time.
Duration: 12 Weeks |
| Comparator Agent |
Ivabradine 5 mg (Run in period) |
The dose will be the same as they were receiving during
screening.
Duration: 01 Week |
| Comparator Agent |
Ivabradine 7.5 mg (Run in period) |
The dose will be the same as they were receiving during
screening.
Duration: 01 Week |
| Intervention |
Test Drug 1: Ivabradine Extended Release Tablets 10 mg |
Each patient will be receiving four tablets in a day (two in morning and two in evening). Patient will be
asked to take the medication on regular basis preferably on same time.
Duration: 12 Weeks |
| Intervention |
Test Drug 2: Ivabradine Extended Release Tablets 15 mg |
Each patient will be receiving four tablets in a day (two in morning and two in evening). Patient will be asked to take the medication on regular basis preferably on same time.
Duration: 12 Weeks |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or female patient aged between 18 and 65 years (both inclusive)
2. Patient who is on stable dose of Ivabradine Tablets 5 mg/ 7.5 mg BD since ≥ 4 weeks for stable chronic heart failure with systolic dysfunction
3. Patient concurrently receiving standard care for stable chronic heart failure (as per recommendation 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure)
4. Patient with stable chronic heart failure of NYHA class II to III for ≥ 4 weeks at the time of screening
5. Patient with sinus rhythm with clinically stable HR > 50 bpm as assessed by automated standard 12 Lead ECG
6. Patient with LVEF ≤ 40 % at screening
7. Patient willing to give informed consent and follow the study protocol
8. Patient with no physical limitation to ingest and retain oral medication
9. Female patient of childbearing potential must be willing to use acceptable method of contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilized, or has not had a hysterectomy at least three months prior to the start of this study). Acceptable method of contraception includes (e.g. barrier method with spermicide). The "calendar method," withdrawal, or an IUD is NOT an acceptable method AND women if postmenopausal (aged greater than 45 years) must have a history of amenorrhea for at least 1 year from the time of last menstrual cycle. |
|
| ExclusionCriteria |
| Details |
1. Patient with history of pacemaker, heart transplantation or on list of heart transplantation
2. Patient with recent (≤ 3 months prior to screening) history of MI, coronary revascularization, stroke, or transient ischemic attack
3. Patient with history of implantable cardioverter defibrillator, or cardiac resynchronization therapy within previous 6 months of screening
4. Patient scheduled for coronary revascularization, or likely to require surgery for valvular disease during the study period
5. Patient with permanent atrial fibrillation or flutter or any other cardiac arrhythmias which may interfere with function of sinoatrial node
6. Patient with sick sinus syndrome, sinoatrial block, congenital long QT or treated with QT prolonging medications, 2nd, 3rd degree and complete atrioventricular block
7. Patient with any cardiac condition which does not justify the inclusion of the patient in the study as per investigator discretion (e.g. acute decompensated heart failure, severe primary valvular disease, active myocarditis, congenital heart disease, peripartum cardiomyopathy etc.)
8. Patient with stroke or transient cerebral ischemia within previous ≤ 3 months prior at screening
9. Patient with current history of unstable or acute HF, unstable angina
10. Patient with severe or uncontrolled hypertension (seated systolic BP [SBP] ≥ 190 mmHg or seated diastolic BP [DBP] ≥ 110 mmHg) uncontrolled hypotension (seated SBP ≤ 90 mmHg or seated DBP ≤ 50 mmHg)
11. Patient with type 2 diabetes (HbA1c ≥ 7%) at screening |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Double Blind Double Dummy |
|
Primary Outcome
|
| Outcome |
TimePoints |
Primary Efficacy Outcome measure:
Change in resting heart rate from baseline (Resting heart rate will be assessed by taking 3 consecutive ECGs taken by automated 12 Lead ECG within 30 minutes after approximately 5-10 minutes of initial rest prior to first ECG recording) |
12 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Secondary Safety Outcome measure:
Proportion of participants with adverse events and serious adverse events |
12 weeks |
Exploratory endpoints
Incidence for hospitalizations for worsening HF, other CV reasons or all-cause mortality from baseline |
12 weeks |
|
|
Target Sample Size
|
Total Sample Size="160"
Sample Size from India="160"
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
|
Phase 3 |
|
Date of First Enrollment (India)
|
15/02/2019 |
| 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
|
Years="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
Not Applicable |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This is randomized, double blind, double dummy, parallel,
multi-centric, comparative phase III
clinical study to evaluate efficacy and safety of Ivabradine Extended Release Tablets in comparison to Ivabradine Tablets in patients with
stable chronic heart failure with systolic dysfunction. Male or female 160 patients (80 patients per group) with age
between 18 to 65 years, on stable dose of Ivabradine Tablets 5 mg/ 7.5 mg BD
since ≥ 4 weeks for stable chronic heart failure with systolic dysfunction. Total study duration of 14 weeks will consist
of 07 visits including: one screening visit, Run in period, one Randomization Visit, three follow-up visits and end
of the study visit. Efficacy analysis will be assessed by change in resting heart rate from baseline to 12 weeks.
Primary
Endpoint(s)
Primary Efficacy Outcome measure
will be:
1. Change in resting heart rate from baseline [Time
frame: 12 weeks]
(Resting
heart rate will be assessed by taking 3 consecutive ECGs taken by automated 12
Lead ECG within 30 minutes after approximately 5-10 minutes of initial rest
prior to first ECG recording)
1. Secondary Safety Outcome measure will be:
Ø Proportion
of participants with adverse events and serious adverse events [Time frame: 12
weeks]
2. Exploratory endpoints
Incidence for hospitalizations for worsening HF, other
CV reasons or all-cause mortality from baseline to 12 weeks |