Clinical trial NCT04575675: Dapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy
Official title: Effects of Dapagliflozin on Hypotensive Patients With Depressed Left Ventricular Ejection Fraction After Sacubitril/Valsartan Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypotension
Heart Failure
Keywords: Heart failure
Dapagliflozin
Sacubitril/valsartan
Lead sponsor: Cheng-Hsin General Hospital
Sponsor class: OTHER
First posted: 2020-10-05
Enrollment: 78
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: 6-minute walking distance
timeFrame: 12 weeks
Secondary outcomes:
measure: EQ-5D-5L
timeFrame: 12 weeks
measure: EQ-Visual analogue scale (EQ-VAS)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
Study officials:
affiliation: Cheng-Hsin General Hospital
name: Hung-Yu Chang, MD
role: PRINCIPAL_INVESTIGATOR
References: