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

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

Study Overview

• Status: Completed
• Conditions: Heart Failure, Systolic
• Intervention / Treatment: Drug: Sacubitril/valsartan

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 75510
      • National Institute of Cardiovascular Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; All 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.	Drug: Sacubitril/valsartan; All 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.; Other Names: Angiotensin receptor blocker and neprilysin inhibitor (ARNI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hypotension	Systolic blood pressure <90 mmHg	12 weeks
Incidence of renal dysfunction	estimated glomerular filtration rate (eGFR) <30 ml/min	12 weeks
Incidence of renal hyperkalemia	Potassium >5.2 mmol/L	12 weeks
Incidence of renal angioedema	Rapid edema, or swelling, of the area beneath the skin or mucosa	12 weeks
Frequency of tolerability	Defined as the dose tolerated by the patients which did not require down titration or discontinuation of prescribed dose during follow-up	During 12 weeks

Collaborators and Investigators

• Sponsor: National Institute of Cardiovascular Diseases, Karachi
• Investigators: Principal Investigator: Muhammad Nauman Khan, FCPS, National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: May 13, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Valsartan; Sacubitril and valsartan sodium hydrate drug combination; Angiotensin Receptor Antagonists
• Other Study ID Numbers: ERC-05/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No