Heart Failure, Systolic
Conditions
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.
Interventions
DRUGSacubitril/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.
Sponsors
National Institute of Cardiovascular Diseases, Pakistan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label non-randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of hypotension | 12 weeks | Systolic blood pressure \<90 mmHg |
| Incidence of renal dysfunction | 12 weeks | estimated glomerular filtration rate (eGFR) \<30 ml/min |
| Incidence of renal hyperkalemia | 12 weeks | Potassium \>5.2 mmol/L |
| Incidence of renal angioedema | 12 weeks | Rapid edema, or swelling, of the area beneath the skin or mucosa |
| 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 |
Countries
Pakistan
Outcome results
None listed