Dapagliflozin in Chronic Heart failure patient

Phase 4

Recruiting

• Conditions: Chronic Heart Failure.; Chronic combined systolic (congestive) and diastolic (congestive) heart failure; I50.42

• Registration Number: IRCT20230331057788N1
• Lead Sponsor: ational University of Medical Sciences

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 1 May 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
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.