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

• Sponsor: National Institute of Cardiovascular Diseases, Karachi (Other)
• Overall Status: Completed
• CT.gov ID: NCT05387967
• Collaborator: (none)
• Enrollment: 121
• Location: 1
• Arm: 1
• Actual Duration (Months): 8.9
• Patients Per Site Per Month: 13.5

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Systolic	Drug: Sacubitril/valsartan	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open label non-randomized clinical trialOpen label non-randomized clinical trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Tolerability of Sacubitril/Valsartan in Heart Failure Patient With Reduced Ejection Fraction
• Actual Study Start Date: Jan 1, 2021
• Actual Primary Completion Date: Jun 30, 2021
• Actual Study Completion Date: Sep 30, 2021

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Incidence of hypotension [12 weeks]

   Systolic blood pressure <90 mmHg

2. Incidence of renal dysfunction [12 weeks]

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

3. Incidence of renal hyperkalemia [12 weeks]

   Potassium >5.2 mmol/L

4. Incidence of renal angioedema [12 weeks]

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

5. Frequency of tolerability [During 12 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institute of Cardiovascular Diseases	Karachi	Sindh	Pakistan	75510

Sponsors and Collaborators

• National Institute of Cardiovascular Diseases, Karachi

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Muhammad Nauman Khan, Assistant Professor of Cardiology, National Institute of Cardiovascular Diseases, Karachi
• ClinicalTrials.gov Identifier: NCT05387967
• Other Study ID Numbers: ERC-05/2020
• First Posted: May 24, 2022
• Last Update Posted: May 24, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Heart Failure; Heart Failure, Systolic; Valsartan; Sacubitril and valsartan sodium hydrate drug combination; Angiotensin Receptor Antagonists

Study Results

No Results Posted as of May 24, 2022