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.
- Conditions
- Other specified rheumatic heart diseases,
- Registration Number
- CTRI/2023/01/049086
- Lead Sponsor
- Sun Pharma Laboratories Limited
- Brief Summary
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|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 If required, dose adjustment/ titration can be done during treatment period but such patients will be withdrawn from the study.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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Yet Recruiting
- Sex
- All
- Target Recruitment
- 240
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- 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.].
- 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.
- 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.
- 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 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.
- 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.
Study & Design
- Study Type
- PMS
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Measures
Name Time Method Change in resting heart rate from baseline 2, 6, 8 and 12 weeks
Trial Locations
- Locations (12)
Avron Hospital
🇮🇳Ahmadabad, GUJARAT, India
Citizen Hospital
🇮🇳Bangalore, KARNATAKA, India
Galaxy Hospital
🇮🇳Varanasi, UTTAR PRADESH, India
Global Hospital
🇮🇳Surat, GUJARAT, India
Grant Govt. Medical College and Sir J.J Group of Hospital
🇮🇳Mumbai, MAHARASHTRA, India
GSVM Medical College
🇮🇳Nagar, UTTAR PRADESH, India
Janta Hospital
🇮🇳Varanasi, UTTAR PRADESH, India
Jawahar Lal Nehru Medical college
🇮🇳Ajmer, RAJASTHAN, India
KIDS Hospital
🇮🇳Khordha, ORISSA, India
Osmania medical college and general hospital
🇮🇳Hyderabad, TELANGANA, India
Scroll for more (2 remaining)Avron Hospital🇮🇳Ahmadabad, GUJARAT, IndiaDr Dhruv JadejaPrincipal investigator9925248209avronhospitalcr@gmail.com