Dapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy

Heart Failure Clinical Trial

Official title:

Effects of Dapagliflozin on Hypotensive Patients With Depressed Left Ventricular Ejection Fraction After Sacubitril/Valsartan Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04575675
• Other study ID #: ChenghsinGH
• Status: Completed
• Phase: Phase 4
• Start date: May 29, 2020
• Est. completion date: December 30, 2020

Study information

• Verified date: July 2021
• Source: Cheng-Hsin General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 30, 2020
• Est. primary completion date: November 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Heart Failure
• Hypotension

Intervention

Drug:
• Dapagliflozin
Dapagliflozin 10mg once daily
• Sacubitril-Valsartan
Sacubitril-Valsartan, maximal tolerated dosage
• Beta blocker
Cardio-selective beta-blocker, including carvedilol, bisoprolol, metoprolol or nebivolol
• Mineralocorticoid Receptor Antagonist
Mineralocorticoid receptor antagonist, including spironolactone or eplerenone

Device:
• Cardiac resynchronization therapy and/or implantable cardioverter defibrillator
CRT-P, CRT-D or ICD if clinically indicated

Locations

Country	Name	City	State
Taiwan	Cheng Hsin General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Cheng-Hsin General Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-minute walking distance	Measuring walking distance within 6 minutes	12 weeks
Secondary	EQ-5D-5L	Measuring health status. Health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.This version of EQ-5D has five-level scale, The number of levels of severity was classified into: having no problems, having slight problems, having moderate problems, having severe problems and being unable to do/having extreme problems. This version can define 3,125 (5x5x5x5x5) different health states.; Valuation of the EQ-5D-5L was then calcuated by the Taiwanese hybrid model, range from -1.0259 to 1. [PLoS One 13(12):e0209344]. Higher score indicates better health status.	12 weeks
Secondary	EQ-Visual analogue scale (EQ-VAS)	Evaluating the participants' overall health status. The participant would be asked to mark health status on the day of the interview on a 20 cm vertical scale with end points of 0 and 100. There are notes at the both ends of the scale that the bottom rate (0) corresponds to " the worst health you can imagine", and the highest rate (100) corresponds to "the best health you can imagine".	12 weeks