Dapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy

July 27, 2021 updated by: Hung-Yu Chang, Cheng-Hsin General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan
        • Cheng Hsin General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dapagliflozin
Dapagliflozin with standard-of-care therapies for heart failure, including sacubitril/valsartan, beta-blocker, MRA, ICD and CRT
Drug: Dapagliflozin
Dapagliflozin 10mg once daily
Other Names:
  • Forxiga
Drug: Sacubitril-Valsartan
Sacubitril-Valsartan, maximal tolerated dosage
Other Names:
  • Entresto
Drug: Beta blocker
Cardio-selective beta-blocker, including carvedilol, bisoprolol, metoprolol or nebivolol
Other Names:
  • Concor, Betaloc zok, Nebilet, Carvedilol
Drug: Mineralocorticoid Receptor Antagonist
Mineralocorticoid receptor antagonist, including spironolactone or eplerenone
Other Names:
  • Aldactin, Inspra
Device: Cardiac resynchronization therapy and/or implantable cardioverter defibrillator
CRT-P, CRT-D or ICD if clinically indicated
Placebo Comparator: Standard of care
Standard-of-care therapies for heart failure, including sacubitril/valsartan, beta-blocker, MRA, ICD and CRT
Drug: Sacubitril-Valsartan
Sacubitril-Valsartan, maximal tolerated dosage
Other Names:
  • Entresto
Drug: Beta blocker
Cardio-selective beta-blocker, including carvedilol, bisoprolol, metoprolol or nebivolol
Other Names:
  • Concor, Betaloc zok, Nebilet, Carvedilol
Drug: Mineralocorticoid Receptor Antagonist
Mineralocorticoid receptor antagonist, including spironolactone or eplerenone
Other Names:
  • Aldactin, Inspra
Device: Cardiac resynchronization therapy and/or implantable cardioverter defibrillator
CRT-P, CRT-D or ICD if clinically indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-minute walking distance
Time Frame: 12 weeks
Measuring walking distance within 6 minutes
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EQ-5D-5L
Time Frame: 12 weeks

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
EQ-Visual analogue scale (EQ-VAS)
Time Frame: 12 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cheng-Hsin General Hospital

Investigators

  • Principal Investigator: Hung-Yu Chang, MD, Cheng-Hsin general hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2020

Primary Completion (Actual)

November 25, 2020

Study Completion (Actual)

December 30, 2020

Study Registration Dates

First Submitted

August 26, 2020

First Submitted That Met QC Criteria

September 29, 2020

First Posted (Actual)

October 5, 2020

Study Record Updates

Last Update Posted (Actual)

August 2, 2021

Last Update Submitted That Met QC Criteria

July 27, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ChenghsinGH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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