search
Back to results

Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure (EMPA-RESPONSE)

Primary Purpose

Heart Failure Acute, Heart Failure，Congestive, Heart Failure; With Decompensation

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Placebo Oral Tablet
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure Acute focused on measuring heart failure, diuretic response, empagliflozin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female >18 years of age; Women of non-child-bearing potential must have a documentation of surgical sterilization (hysterectomy and/or bilateral oophorectomy) OR must have experienced menopause (no menses for >12 months). Women of child bearing potential must have a negative pregnancy test, AND must use highly effective methods of contraception during treatment with IP plus 5 days after the end of study drug administration.

  • Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening:

    1. Dyspnea at rest or with minimal exertion
    2. Signs of congestion, such as edema, rales, and/or congestion on chest radiograph
    3. BNP ≥350 pg/mL or NT-proBNP ≥1,400 pg/mL (for patients with AF: BNP≥500 pg/mL or NT-proBNP ≥2,000 pg/mL)
    4. Treated with loop diuretics at screening
  • Able to be randomized within 24 hours from presentation to the hospital
  • Able and willing to provide freely given written informed consent
  • eGFR (CKD-EPI) ≥30 ml/min/1.73m2 between presentation and randomization

Exclusion Criteria:

  • Diabetes Mellitus Type I
  • Dyspnea primarily due to non-cardiac causes
  • Cardiogenic shock
  • Acute coronary syndrome within 30 days prior to randomization
  • Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization
  • Signs of keto-acidosis and/or hyperosmolar hyperglaecemic syndrome (pH>7.30 and glucose >15 mmol/L and HCO3>18 mmol/L)
  • Pregnant or nursing (lactating) women
  • Current participation in any interventional study
  • Inability to follow instructions or comply with follow-up procedures
  • Any other medical conditions that may put the patient at risk or influence study results in the investigator's opinion, or that the investigator deems unsuitable for the study.

Sites / Locations

  • Jeroen Bosch Ziekenhuis
  • TREANT Zorggroep
  • Antonius Ziekenhuis
  • ISALA Klinieken
  • University Medical Center Groningen

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Empagliflozin

Placebo

Arm Description

Empagliflozin 10 mg daily, oral, 30 days

Matching Placebo 10 mg daily, oral, 30 days

Outcomes

Primary Outcome Measures

Dyspnea
Change in Dyspnea on VAS analogue scale (AUC) VAS Score is a measure/scale where patients on a scale from 0 to 100 can assign their current dyspnea score. 0 means there can be no worse dyspnea, 100 means it cannot get any better (perfect). The change in Dyspnea VAS means higher score is better outcomes. Individual changes in VAS score are be visualized (virtually) as a curve where the X-axis shows study day baseline to day 4, and y-axis shows VAS score. Using this approach, area under the curves for each study day (trapezoids) can be calculated, and added together, resulting in an overall VAS AUC score (mmxh) and change in VAS can be caculated
Diuretic Response
Weight change from baseline per 40 mg of Furosemide equivalent
Length of Stay
Hospital stay of Index admission
Plasma NTproBNP
Change in NTproBNP

Secondary Outcome Measures

Death and/or Heart Failure Re-admission
Death and/or heart failure re-admission at day 30
Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60
Inhospital Worsening Heart Failure or All Cause mortality or Heart Failure Readmission at day 60
All Cause Mortality
All Cause Mortality at 60 days

Full Information

First Posted
June 23, 2017
Last Updated
February 9, 2020
Sponsor
University Medical Center Groningen
search

1. Study Identification

Unique Protocol Identification Number
NCT03200860
Brief Title
Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure
Acronym
EMPA-RESPONSE
Official Title
Randomized, Double Blind, Placebo Controlled, Multicenter Pilot Study on the Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure (EMPA-RESPONSE-AHF)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
December 18, 2017 (Actual)
Primary Completion Date
September 18, 2019 (Actual)
Study Completion Date
September 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Acute decompensated heart failure is the fastest growing disease in the world and the leading cause of hospital admissions worldwide. Short term mortality and rehospitalization are extremely high (20-30% within 3-6 months) and there is no therapy available that improves clinical outcome in these patients. Empagliflozin is a selective inhibitor of sodium glucose co-transporter with diuretic and renal- protective properties. In patients with type 2 diabetes at high risk for cardiovascular events, empagliflozin reduced the risk of hospitalization for heart failure by 35%. Based on the promising pharmacological profile of empagliflozin in relation to the needs for treatment of acute decompensated heart failure, we hypothesize that empagliflozin exerts positive effects in acute decompensated heart failure, with or without diabetes, This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study in subjects admitted for acute decompensated heart failure. Eighty eligible subjects will be randomized in a 1:1 ratio to receive either empagliflozin 10 mg/day or matched placebo.
Detailed Description
This is a randomized, placebo-controlled, double-blind, parallel group, multicenter study in subjects admitted for acute decompensated heart failure. Eighty eligible subjects will be randomized in a 1:1 ratio to receive either empagliflozin 10 mg/day or matched placebo. Treatment will be continued until 30 days after index event, and primary efficacy measurements will be carried out during hospitalization and safety events until 60 days after index hospitalisation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure Acute, Heart Failure，Congestive, Heart Failure; With Decompensation
Keywords
heart failure, diuretic response, empagliflozin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized, placebo-controlled, double-blind, parallel group, multicenter study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double blind, placebo controlled
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin
Arm Type
Active Comparator
Arm Description
Empagliflozin 10 mg daily, oral, 30 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo 10 mg daily, oral, 30 days
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Intervention Description
10 mg daily, oral, 30 days
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Matching Placebo, 10 mg daily, oral, 30 days
Primary Outcome Measure Information:
Title
Dyspnea
Description
Change in Dyspnea on VAS analogue scale (AUC) VAS Score is a measure/scale where patients on a scale from 0 to 100 can assign their current dyspnea score. 0 means there can be no worse dyspnea, 100 means it cannot get any better (perfect). The change in Dyspnea VAS means higher score is better outcomes. Individual changes in VAS score are be visualized (virtually) as a curve where the X-axis shows study day baseline to day 4, and y-axis shows VAS score. Using this approach, area under the curves for each study day (trapezoids) can be calculated, and added together, resulting in an overall VAS AUC score (mmxh) and change in VAS can be caculated
Time Frame
From baseline to Day 4
Title
Diuretic Response
Description
Weight change from baseline per 40 mg of Furosemide equivalent
Time Frame
Total weight change from baseline to Day 4
Title
Length of Stay
Description
Hospital stay of Index admission
Time Frame
within 60 days
Title
Plasma NTproBNP
Description
Change in NTproBNP
Time Frame
From baseline to Day 4
Secondary Outcome Measure Information:
Title
Death and/or Heart Failure Re-admission
Description
Death and/or heart failure re-admission at day 30
Time Frame
Day 30
Title
Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60
Description
Inhospital Worsening Heart Failure or All Cause mortality or Heart Failure Readmission at day 60
Time Frame
60 days
Title
All Cause Mortality
Description
All Cause Mortality at 60 days
Time Frame
60 day
Other Pre-specified Outcome Measures:
Title
Serious Adverse Events
Description
SAE including all cause mortality. Per request Clintrials.gov different from Protocol definition
Time Frame
60 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female >18 years of age; Women of non-child-bearing potential must have a documentation of surgical sterilization (hysterectomy and/or bilateral oophorectomy) OR must have experienced menopause (no menses for >12 months). Women of child bearing potential must have a negative pregnancy test, AND must use highly effective methods of contraception during treatment with IP plus 5 days after the end of study drug administration. Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening: Dyspnea at rest or with minimal exertion Signs of congestion, such as edema, rales, and/or congestion on chest radiograph BNP ≥350 pg/mL or NT-proBNP ≥1,400 pg/mL (for patients with AF: BNP≥500 pg/mL or NT-proBNP ≥2,000 pg/mL) Treated with loop diuretics at screening Able to be randomized within 24 hours from presentation to the hospital Able and willing to provide freely given written informed consent eGFR (CKD-EPI) ≥30 ml/min/1.73m2 between presentation and randomization Exclusion Criteria: Diabetes Mellitus Type I Dyspnea primarily due to non-cardiac causes Cardiogenic shock Acute coronary syndrome within 30 days prior to randomization Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization Signs of keto-acidosis and/or hyperosmolar hyperglaecemic syndrome (pH>7.30 and glucose >15 mmol/L and HCO3>18 mmol/L) Pregnant or nursing (lactating) women Current participation in any interventional study Inability to follow instructions or comply with follow-up procedures Any other medical conditions that may put the patient at risk or influence study results in the investigator's opinion, or that the investigator deems unsuitable for the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adriaan Voors, Prof. Dr.
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jeroen Bosch Ziekenhuis
City
Den Bosch
State/Province
Brabant
Country
Netherlands
Facility Name
TREANT Zorggroep
City
Emmen
State/Province
Drenthe
Country
Netherlands
Facility Name
Antonius Ziekenhuis
City
Sneek
State/Province
Friesland
Country
Netherlands
Facility Name
ISALA Klinieken
City
Zwolle
State/Province
Overijssel
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700RB
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26378978
Citation
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.
Results Reference
background
PubMed Identifier
27299675
Citation
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.
Results Reference
background

Learn more about this trial

Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure

We'll reach out to this number within 24 hrs