]>
IRCT20230331057788N1 IRCT 2023-04-04 National University of Medical Sciences Dapagliflozin in Chronic Heart failure patient CLINICAL EFFICACY OF DAPAGLIFLOZIN IN ASSOCIATION WITH GENETIC POLYMORPHISM AND ITS PLASMA LEVELS IN CHRONIC HEART FAILURE PATIENTS 2023-04-10 anticipated 170 Complete https://irct.ir/trial/69370 interventional Randomization: Randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: Patients will be randomized on basis of computer- generated random numbers. Each patient will be given a particular code number. 4 Chronic Heart Failure. Intervention 1: Experimental Group: (n=85), This group will receive intervention of drug Dapagliflozin (10mg) daily orally in addition to guideline directed medical therapy (GDMT) in Chronic heart failure patients. Intervention 2: Control group: This group will receive only guideline directed medical therapy GDMT in chronic heart failure patients. No - There is not a plan to make this available Justification or reason for not sharing IPD is Data of Army Personnel can not be shared due to security reasons.
public Dr. Saima Rafique
Army Medical College, Abid Majeed Road, Rawalpindi Cantt
Rawalpindi Pakistan 46000 +92 51 5516755 saimarafiqu34@gmail.com Army Medical College, National University of Medical Sciences scientific Saima Rafique
Army Medical College, Abid Majeed Road, Rawalpindi Cantt
Rawalpindi Pakistan 74600 +92 51 5516755 saimarafiqu34@gmail.com Army Medical College, National University of Medical Sciences, Pakistan Pakistan Pakistani patients of 18 years and above, males and females Diagnosed symptomatic heart failure (NYHA class 1–IV) Ejection fraction (EF) ≤ 40% on imaging study within last 12 months prior to enrolment Patient on stable GDMT of heart failure for ≥4 weeks Both diabetic and non-diabetic patients no limit no limit Both Type-1 diabetics or patients having any history of DKA Patients having eGFR ≤ 25 ml/ min/ 1.73 m2 as per (CKD-EPI formula), systolic blood pressure (SBP) < 95 mmHg Patients having MI, unstable angina, stroke, acute heart failure (HF) or any hospitalization due to acute HF <4 weeks preceding enrolment Patients undergoing PCI /CABG or valvular replacement, any previous transplantation of heart or infixing of ventricular assistance device (VAD), implantation of Cardiac resynchronization therapy (CRT) within 3 months preceding enrolment or any plan to undergo after randomization Patients having active myocarditis, uncorrected primary valvular disease, restrictive or hypertrophic (obstructive) cardiomyopathy; bradycardia, 2nd or 3rd degree heart block without having any pacemaker Patients received any SGLT2i within 12 weeks preceding screening visit or hypersensitivity to Dapagliflozin Pregnant ladies and nursing mothers, severe COPD leading to dyspnea, any malignancy or hepatic impairment I50.42 Chronic combined systolic (congestive) and diastolic (congestive) heart failure Treatment - Drugs Treatment - Drugs Experimental Group: (n=85), This group will receive intervention of drug Dapagliflozin (10mg) daily orally in addition to guideline directed medical therapy (GDMT) in Chronic heart failure patients Control group: This group will receive only guideline directed medical therapy GDMT in chronic heart failure patients Primary outcome will include exploration of clinical efficacy of Dapagliflozin in CHF patients. Timepoint: At day 0 and after 12 weeks. Method of measurement: By biochemical parameters including (BNP/ NT-pro BNP, serum uric acid, creatinine, HbA1c, urine R/E, spot urine P/C ratio, echocardiography), improvement in quality of life by KCCQ questionnaire, NYHA functional class. SAFETY ANALYSIS OF DAPAGLIFLOZIN will be analyzed by observing number of events of major hypoglycemia, hypotension urogenital infection, fournier’s gangrene, DKA and any amputation before and after intervention. MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) including heart failure hopsitalisations, urgent heart failure visits, stroke, arrhythmia, MI, acute kidney injury and cardiogenic death will be observed for a number of episodes before and after intervention with Dapagliflozin. 1)To determine the prevalence of Dapagliflozin transporter genes SLC5A2 for its single nucleotide polymorphism (SNPs) of SLC5A2 (rs3813008 G>A ,rs9934336 G > A and rs3116150 G>A) encoding SGLT2 transporter in Pakistani CHF population. 2)To estimate steady state plasma drug levels of Dapagliflozin and evaluate association of (SNPs) of Dapagliflozin transporter genes on steady state concentration in Pakistani CHF patients.3)To evaluate association of SNPs and plasma levels of Dapagliflozin with clinical efficacy in Pakistani CHF patients. Timepoint: After intervention of 12 weeks with Dapagliflozin. Method of measurement: Polymerase Chain Reaction (PCR) will be performed for genetic analysis of SNPs of SLC5A2 (rs3813008 G>A and rs3116150 G>A) followed by Restriction Fragment Length Polymorphism (RFLP). Allele Specific- Polymerase Chain Reaction (AS-PCR) will be performed for genotyping of variant allele (rs9934336 G>A) of SLC5A2. Drug levels will be estimated by HPLC. National University of Medical Sciences Approved 2023-01-06 Ethical Review Committee Army Medical College, Abid Majeed Road, Rawalpindi Cantt Rawalpindi Punjab Pakistan