Dapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy

NCT ID: NCT04575675

Last Updated: 2021-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-29
• Study Completion Date: 2020-12-30

Brief Summary

The DAPA-HF trial demonstrated that dapagliflozin was able to reduce the risk of worsening heart failure events and cardiovascular death comparing to placebo in patients with reduced ejection fraction further to standard of care. However, hypotensive patients who generally have higher risks comparing to normotensive patients, were under represented in the DAPA-HF. The investigators aimed to evaluate clinical effects of dapagliflozin on hypotensive heart failure patients receiving chronic sacubitril/valsartan treatment.

Detailed Description

The DAPA-HF trial demonstrated that dapagliflozin was able to reduce the risk of worsening heart failure (HF) events and cardiovascular death comparing to placebo in patients with reduced ejection fraction further to standard of care. However, hypotensive patients who generally have higher risks comparing to normotensive patients, were under represented in the DAPA-HF. The investigators aimed to evaluate clinical effects of dapagliflozin on hypotensive HFrEF patients receiving chronic sacubitril/valsartan (Sal/Val) treatment.

This is an investigator-initiated, interventional, prospective. open-label study. The inclusion criteria were (1) chronic symptomatic HF with New York Heart Association (NYHA) class II-IV and LVEF less than 40%, (2) treatment with stable and maximal tolerable dose of Sac/Val, beta-blocker with or without mineralocorticoid receptor antagonist (MRA), (3) 6-minute walking-distance (6MWD)≥ 100meters and ≤425 meters at enrollment, (4) systolic blood pressure ≤100 mmHg at enrollment. The exclusion criteria were (1) type 1 diabetes mellitus, (2) patients previously treated with any sodium glucose co-transporter 2 inhibitor (SGLT2i).

After applying the inclusion and exclusion criteria, if the participants had type 2 diabetes mellitus, the participants will receive dapagliflozin 10mg daily directly. If the participants did not have history of diabetes mellitus, the participants will be allocated to either receiving dapagliflozin 10mg daily or receiving standard heart failure treatment without dapagliflozin.

Vital signs and laboratory tests were examined at baseline, 2-week, 4-week and 12-week. Six-minute-walking-test, five-level EuroQol five dimensions (EQ-5D-5L) questionnaire and visual analogue scale (VAS) were collected at baseline and at 12-week.

Conditions

Hypotension; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dapagliflozin

Dapagliflozin with standard-of-care therapies for heart failure, including sacubitril/valsartan, beta-blocker, MRA, ICD and CRT

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Dapagliflozin 10mg once daily

Sacubitril-Valsartan

Intervention Type: DRUG

Sacubitril-Valsartan, maximal tolerated dosage

Beta blocker

Intervention Type: DRUG

Cardio-selective beta-blocker, including carvedilol, bisoprolol, metoprolol or nebivolol

Mineralocorticoid Receptor Antagonist

Intervention Type: DRUG

Mineralocorticoid receptor antagonist, including spironolactone or eplerenone

Cardiac resynchronization therapy and/or implantable cardioverter defibrillator

Intervention Type: DEVICE

CRT-P, CRT-D or ICD if clinically indicated

Standard of care

Standard-of-care therapies for heart failure, including sacubitril/valsartan, beta-blocker, MRA, ICD and CRT

Group Type: PLACEBO_COMPARATOR

Sacubitril-Valsartan

Intervention Type: DRUG

Sacubitril-Valsartan, maximal tolerated dosage

Beta blocker

Intervention Type: DRUG

Cardio-selective beta-blocker, including carvedilol, bisoprolol, metoprolol or nebivolol

Mineralocorticoid Receptor Antagonist

Intervention Type: DRUG

Mineralocorticoid receptor antagonist, including spironolactone or eplerenone

Cardiac resynchronization therapy and/or implantable cardioverter defibrillator

Intervention Type: DEVICE

CRT-P, CRT-D or ICD if clinically indicated

Interventions

Dapagliflozin

Dapagliflozin 10mg once daily

Intervention Type: DRUG

Sacubitril-Valsartan

Sacubitril-Valsartan, maximal tolerated dosage

Intervention Type: DRUG

Beta blocker

Cardio-selective beta-blocker, including carvedilol, bisoprolol, metoprolol or nebivolol

Intervention Type: DRUG

Mineralocorticoid Receptor Antagonist

Mineralocorticoid receptor antagonist, including spironolactone or eplerenone

Intervention Type: DRUG

Cardiac resynchronization therapy and/or implantable cardioverter defibrillator

CRT-P, CRT-D or ICD if clinically indicated

Intervention Type: DEVICE

Other Intervention Names

Forxiga; Entresto; Concor, Betaloc zok, Nebilet, Carvedilol; Aldactin, Inspra

Eligibility Criteria

Inclusion Criteria

• chronic symptomatic HF with New York Heart Association (NYHA) class II-IV and left ventricular ejection fraction (LVEF) less than 40%
• treatment with stable and maximal tolerable dose of Sac/Val, beta-blocker with or without mineralocorticoid receptor antagonist
• 6-minute walking-distance (6MWD)≥ 100meters and ≤425 meters at enrollment
• systolic blood pressure ≤100 mmHg at enrollment

Exclusion Criteria

• hemodialysis
• severe co-morbidities with life expectancy less than 1 year
• type 1 diabetes mellitus
• ever treated with any type of sodium glucose cotransporter 2 inhibitor (SGLT2i)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cheng-Hsin General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hung-Yu Chang

Attending Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hung-Yu Chang, MD

Role: PRINCIPAL_INVESTIGATOR

Cheng-Hsin General Hospital

Locations

Cheng Hsin General Hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

ChenghsinGH

Identifier Type: -

Identifier Source: org_study_id