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Safety and Tolerability of Sacubitril/Valsartan in Heart Failure Patient With Reduced Ejection Fraction

Phase 4
Completed
Conditions
Heart Failure, Systolic
Interventions
Registration Number
NCT05387967
Lead Sponsor
National Institute of Cardiovascular Diseases, Pakistan
Brief Summary

This proof-of-concept, open-label non-randomized clinical trial was conducted at a tertiary care cardiac center in Karachi, Pakistan. Patients with HFrEF were prescribed Sacubitril/Valsartan and followed for 12 weeks for the assessment of safety and tolerability. Safety measures included incidence of hypotension, renal dysfunction, hyperkalemia, and angioedema

Detailed Description

A required number of consecutive patients meeting the inclusion criteria were recruited for this study. After written informed consent patient demographic and baseline clinical characteristics were obtained. Inclusion criteria for the study were either gender between 18 to 80 years of age, diagnosed with congestive heart failure (CHF) with NYHA class II-IV, and LVEF ≤ 40%. Pre-inclusion safety parameters were patients who were stable on any dose of beta-blockers, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) prior to enrolment in the study. Patients with a baseline diagnosis of Hyperkalemia, hypotension, renal dysfunction, and a history of hypersensitivity to the active substances, Sacubitril/Valsartan, or to any of the excipients or drugs of similar chemical classes were excluded from the study.

All the recruited patients were prescribed Sacubitril/Valsartan 100mg/200mg twice a day (BID) for 6 weeks. A weekly telephonic follow-up was made to assess the patient's medication adherence level using the Dose-Nonadherence scale. All the patients were kept under a close follow-up for 6 weeks period and at the end of 12 weeks of medication, the safety and tolerability outcomes were assessed as per the operational definition.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
121
Inclusion Criteria
  • Either gender
  • between 18 to 80 years of age
  • Diagnosed with Heart failure with reduced ejection fraction (HFrEF)
  • New York Heart Association (NYHA) class II-IV
  • Left ventricular ejection fraction (LVEF) ≤ 40%
  • Stable on any dose of beta-blockers, ACEI or ARB
Exclusion Criteria
  • Refused to participate in the study
  • Patients with hyperkalemia
  • Patients with hypotension
  • Patients with renal dysfunction
  • History of hypersensitivity to the active substances, Sacubitril/Valsartan, or to any of the excipients or drugs of similar chemical classes

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment groupSacubitril/valsartanAll the recruited patients were prescribed Sacubitril/Valsartan at a starting dose of 50 (24/26) mg BID which was up-titrated, over the period of initial 6 weeks, to the maximum tolerated dose up to 200 (97/103) mg BID and further followed for a total of 12 weeks.
Primary Outcome Measures
NameTimeMethod
Frequency of tolerabilityDuring 12 weeks

Defined as the dose tolerated by the patients which did not require down titration or discontinuation of prescribed dose during follow-up

Incidence of renal dysfunction12 weeks

estimated glomerular filtration rate (eGFR) \<30 ml/min

Incidence of hypotension12 weeks

Systolic blood pressure \<90 mmHg

Incidence of renal hyperkalemia12 weeks

Potassium \>5.2 mmol/L

Incidence of renal angioedema12 weeks

Rapid edema, or swelling, of the area beneath the skin or mucosa

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

National Institute of Cardiovascular Diseases

🇵🇰

Karachi, Sindh, Pakistan

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