CTRI/2023/01/049086 [Registered on: 18/01/2023] Trial Registered Prospectively
Last Modified On:
17/01/2023
Post Graduate Thesis
No
Type of Trial
PMS
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A clinical trial to study the effects of combination drug as substitution therapy in patients suffering from Stable Chronic Heart Failure (CHF) with Systolic Dysfunction or in Patients of Stable Chronic Angina Pectoris.
Scientific Title of Study
A Multicentric, Phase IV Clinical Trial to Evaluate Safety and Efficacy of Fixed Dose Combination of Carvedilol and Ivabradine Hydrochloride Tablet as a Substitution Therapy in Patients of Stable Chronic Heart Failure (CHF) with Systolic Dysfunction or in Patients of Stable Chronic Angina Pectoris.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ICR/20/016 Version No. 2.0 Dated 25/FEB/2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pravin Ghadge
Designation
Head-India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai MAHARASHTRA 400063 India
Phone
02243245598
Fax
02243244343
Email
pravin.ghadge@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Pravin Ghadge
Designation
Head- India Clinical Research
Affiliation
Sun Pharma Laboratories Ltd
Address
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
Pravin.Ghadge@sunpharma.com
Details of Contact Person Public Query
Name
Mr Mihir Pandya
Designation
Senior Project Manager
Affiliation
Let’s Evolve Life Pvt. Ltd
Address
708, Shivalik Shilp,
Nr. Iskcon Cross Road,
Ahmedabad, Gujarat-380015, India
Ahmadabad GUJARAT 380015 India
Phone
7984207030
Fax
Email
mihirpandya@letsevolvelife.com
Source of Monetary or Material Support
Sun Pharma Laboratories Limited
Tandalja, Vadodara-390020,
Gujarat, India.
Primary Sponsor
Name
Sun Pharma Laboratories Limited
Address
Tandalja, Vadodara-390020,
Gujarat, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 12
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Dhruv Jadeja
Avron Hospital
04 Shantiniketan park, Department of Cardiology, Ground floor, Near Sardar Patel Colony, Naranpura, Ahmedabad-380013. Ahmadabad GUJARAT
9925248209
avronhospitalcr@gmail.com
Dr Ambanna Gowda
Citizen Hospital
Number 14, 2nd main , Dispensary, Department of general medicine Road,Kalasipalya, Bangalore 560002 Bangalore KARNATAKA
9845270377
dr.ambanagowda@gmail.com
Dr Ajay Kumar Pandey
Galaxy Hospital
Dayal Enclave, Department of Cardiology, Ground floor, 4,5,6,7, Mahmoorganj Rd, Near Railway Station, Mahmoorganj, Varanasi, Uttar Pradesh 221010 Varanasi UTTAR PRADESH
9415202323
dr.akpandeycardio@gmail.com
Dr Milan Dhaduk
Global Hospital
4th floor, Department of Cardiology, Global point beside Narjiran Restaurant , Sarthana , Jakat Naka 395006, Surat Surat GUJARAT
8866683338
drmilandhadukcr@gmail.com
Dr Hemant Ramsharan Gupta
Grant Govt. Medical College and Sir J.J Group of Hospital
OPD No 20, Department of Internal Medicine, old OPD building,Byculla, Mumbai-400008.
Mumbai MAHARASHTRA
9870456888
drhemantgupta@hotmail.com
Dr Mohammad Mahmodullah Razi
GSVM Medical College
Room No.14, 3rd Floor, LPS Institute Of Cardiology, Near Gol Churaha, Swaroop Nagar, Kanpur-208002 U.P. India. Kanpur Nagar UTTAR PRADESH
7408427786
drmmrazi@gmail.com
Dr Sudhakar Singh
Janta Hospital
Department of Cardiology, Ground floor, Amra- Akhri Road, Bypass, Chunar Rd, near Pani Tanki, Varanasi, Uttar Pradesh 221011 Varanasi UTTAR PRADESH
9088054684
sudhakar.harsh@gmail.com
Dr Sanjiv Maheshwari
Jawahar Lal Nehru Medical college
Department of Cardiology, Ground floor, Kala Bagh, Ajmer -305001. Ajmer RAJASTHAN
9460479888
doctor.sanjiv@gmail.com
Dr Manabhanjan Jena
KIDS Hospital
Plot no 1120, Department of Cardiology, Ground floor, Dumduma, Bhubaneshwar, Odisha, 751019 Khordha ORISSA
8336844717
jena.mana@gmail.com
Dr P Krishnamala Konda Reddy
Osmania medical college and general hospital
Department of Cardiology, 2nd floor, Afzalgunj, Hyderabad, T.S 500012, India Hyderabad TELANGANA
9848015098
drkmkreddyp@yahoo.com
Dr Chirag Mangaldas Patel
Pagarav Hospital & ICU
Plot No. 512/1, Cardiology department, Nr. G-6 Circle, Opp. SBI,Sector 23-Gandhinagar-382023, Gujarat, India Gandhinagar GUJARAT
One tablet twice daily, once in the morning and once in the evening.
for 12 Weeks
Comparator Agent
NIL
NIL
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1) Patient of either gender, aged 18 to 65 years (both inclusive) and ready to give written informed consent to participate in the study at the time of screening
2) Criteria specific for Stable Chronic Heart Failure (CHF) at screening
• Patient with history of clinically stable chronic heart failure (NYHA class II to IV) with left ventricular systolic dysfunction for ≥ 4 weeks prior to screening
• Patient with LVEF ≤ 35%
• Patient concurrently receiving standard of care for chronic heart failure at stable doses for at least one month
3) Criteria specific for Stable Chronic Angina Pectoris at screening
• Patient with history of clinically stable chronic angina pectoris for at least 3 months prior to screening
• Patient with coronary artery disease (documented by previous myocardial infarction, previous percutaneous or surgical coronary revascularisation, or angiographic evidence that one or more major coronary arteries had narrowed by 50% or more)
• Patient concurrently receiving standard of care for Chronic Angina Pectoris at stable doses for at least one month
4) Patient with sinus rhythm with clinically stable HR > 50 bpm as assessed by automated standard 12 Lead ECG
5) Patient taking Carvedilol 3.125/6.25/12.5 mg BID and Ivabradine 5 mg BID concomitantly and suitable for substitution therapy at same dose level
6) Patient with no physical limitation to ingest and retain oral medication
7) Women of childbearing potential must have a negative urine pregnancy test prior to study entry and agree to use highly effective methods of contraception to prevent pregnancy from study entry till at least two weeks after the last dose of the study medication (such contraception may include hormonal birth control e.g., combined estrogen and progestogen containing [oral, intravaginal, or transdermal] or progesterone only [oral, injectable, or implantable] hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone releasing system OR bilateral tubal occlusion, vasectomized partner, or total sexual abstinence)
[Note: Women with childbearing potential are defined as: those who are not (1) surgically sterile (bilateral oophorectomy, hysterectomy, or bilateral tubal ligation) or (2) post-menopausal. Post-
menopausal woman will be defined as: Woman not using hormonal replacement therapy and have had at least 12 continuous months of natural (spontaneous) amenorrhea and be greater than 45 years of age.]
ExclusionCriteria
Details
1. Patient who is Pacemaker dependent (heart rate imposed exclusively by the pacemaker) or with history of pacemaker, heart transplantation or on list of heart transplantation
2. Patient with permanent atrial fibrillation or flutter or any other cardiac arrhythmias which may interfere with function of sinoatrial node
3. Patient with sick sinus syndrome, sinoatrial block, congenital long QT or 2nd, 3rd degree and complete atrioventricular block
4. Patient with stroke or transient cerebral ischemia within 3 months prior to screening
5. Patient with unstable/decompensated or acute HF, Prinzmetal’s angina
6. Acute myocardial infarction, Cardiogenic shock, Severe peripheral vascular disease (e.g. Raynaud’s phenomenon)
7. Patient with severe hypotension (seated systolic blood pressure <90 mmHg, seated diastolic blood pressure <50 mmHg)
8. Patient with uncontrolled hypertension (SeSBP ≥ 160 or SeDBP ≥ 100 mmHg) or uncontrolled diabetes (HbA1c ˃ 9%)
9. Patient with chronic obstructive pulmonary disease associated with bronchial obstruction or with history of bronchospasm or asthma
10. Patient with metabolic acidosis, untreated phaeochromocytoma
11. Patient with labile or secondary hypertension, orthostatic hypotension, acute myocarditis, a haemodynamically relevant stenosis of the heart valves or ventricular outflow tract, end-stage peripheral arterial disease or who are concomitantly receiving an α1-receptor antagonist or α2-receptor agonist.
12. Patient with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
13. Patient with sever hepatic impairment (Child Pugh Class C), sever renal impairment (eGFR < 15 ml/min)
14. Patient with history of psychiatric disorders (as per DSM-5) which may interfere with patient’s ability to understand or complete requirements of the study
15. Patient who is on strong cytochrome P450 3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin per os, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir), nefazodone and grapefruit juice.
16. Patient treated with QT prolonging medications (e.g. quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, intravenous erythromycin), intravenous antiarrhythmic agents
17. Patient with moderate CYP3A4 inhibitors (verapamil or diltiazem) with heart rate reducing properties
18. Patient with history of HIV and /or Hepatitis B and /or Hepatitis C
19. Patient with current or recent substance abuse, including alcohol (as per DSM-5)
20. Pregnant or lactating woman
21. Surgical or medical condition that, in the judgment of the Investigator that could interfere with absorption, distribution, metabolism, or excretion of the investigational products to be used.
22. Patient who is hypersensitive to active substance, any other beta-blockers or to any of the excipients of this formulation
23. Participation in any experimental drug and/or device study within 60 days before screening
24. Patient judged unfit for this study by investigator
25. Patient with clinically significant disorder that, in the opinion of the investigator, would result in jeopardizing patient’s safety and efficacy of the drug
26. Investigator, study personnel, sponsor representatives and their first degree relatives
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Safety assessment includes Treatment Emergent Adverse Events (TEAEs) (Bradycardia, Dizziness and Visual Disturbances) reported during the study
baseline, 2 weeks,6 weeks, 8 weeks and 12 weeks
Secondary Outcome
Outcome
TimePoints
Change in resting heart rate from baseline
2, 6, 8 and 12 weeks
Target Sample Size
Total Sample Size="240" Sample Size from India="240" 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
Post Marketing Surveillance
Date of First Enrollment (India)
30/01/2023
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="0" Months="4" Days="0"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
NIL
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
is a single arm, open label, multi-centric study. The study will be conducted
at approximately 12-15 number of centres in India, having qualified
Investigators. The study will be initiated only after the receipt of
regulatory and ethics committee (EC) approval.
After
obtaining the informed consent, patient will be screened by undergoing
various assessments as mentioned in Schedule of Assessment (Appendix I).
After completion of screening period and confirming eligibility, patient will
be enrolled by allotting enrollment number. Patient taking Carvedilol 3.125
mg OR 6.25 mg OR 12.5 mg BID concomitantly with Ivabradine 5 mg
BID will receive Fixed Dose Combination of Carvedilol and Ivabradine
Hydrochloride Tablet (3.125 + 5 mg) OR (6.25 mg + 5 mg) OR (12.5
mg + 5 mg) twice daily respectively for 12 weeks of treatment period. If
required, dose adjustment/ titration can be done during treatment period but
such patients will be withdrawn from the study.
The
study has following visits:
Visit
1: Screening Period (2 weeks, Day -14 to -1)
Visit
2: Enrollment Visit (Week 1, Day 1)
Visit
3: Week 2, Day 14 ± 2
Visit
4: Week 6, Day 42 ± 2
Visit
5: Week 8, Day 56 ± 2
Visit
6: End of Study Visit (Week 12, Day 84 ± 2)
Patients
will be provided with diary to record details about study drug administration
and adverse events. Patients will be instructed to bring completed diary at
each visit. Patients discontinuing early from the study should complete the
assessments mentioned under Visit 6 (Week 12).