Heart Failure AcutePhase 2EMPA-RESPONSENCT03200860

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

A Phase 2 study testing Empagliflozin 10 MG in people with Heart Failure Acute and Heart Failure，Congestive, run by University Medical Center Groningen at 5 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure Acute, Heart Failure，Congestive, Heart Failure; With Decompensation
What is being tested?: Empagliflozin 10 MG
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 80 participants
Where: 5 sitesNetherlands
Study dates: 18 Dec 2017to 18 Sep 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 9Show fewer

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

Who cannot join

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)

Show all 10Show fewer

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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Netherlands5 sites

Jeroen Bosch Ziekenhuis
's-Hertogenbosch, North Brabant
TREANT Zorggroep
Emmen, Drenthe
University Medical Center Groningen
Groningen, 9700RB
Antonius Ziekenhuis
Sneek, Provincie Friesland
ISALA Klinieken
Zwolle, Overijssel

Other trials in Netherlands

About this study

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)

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.

Read the detailed description

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.

Conditions: Heart Failure Acute, Heart Failure，Congestive, Heart Failure; With Decompensation
Being tested: Empagliflozin 10 MG, Placebo Oral Tablet
Keywords: heart failure, diuretic response, empagliflozin
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Empagliflozin 10 MGDrug
10 mg daily, oral, 30 days
Placebo Oral TabletDrug
Matching Placebo, 10 mg daily, oral, 30 days

Study groups in NCT03200860
Study group	Role	What they receive
Empagliflozin	Active comparator	Empagliflozin 10 mg daily, oral, 30 days Receives: Drug: Empagliflozin 10 MG
Placebo	Placebo comparator	Matching Placebo 10 mg daily, oral, 30 days Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: From baseline to Day 4
Diuretic Response
Weight change from baseline per 40 mg of Furosemide equivalent
Measured: Total weight change from baseline to Day 4
Length of Stay
Hospital stay of Index admission
Measured: within 60 days
Plasma NTproBNP
Change in NTproBNP
Measured: From baseline to Day 4

Secondary outcomes (3)

Death and/or Heart Failure Re-admission
Death and/or heart failure re-admission at day 30
Measured: 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
Measured: 60 days
All Cause Mortality
All Cause Mortality at 60 days
Measured: 60 day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Dec 201718 Sep 2019

First posted27 Jun 2017
Study start18 Dec 2017
Primary completion18 Sep 2019
Study completion18 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Heart Failure AcuteStudies of the same condition, open and under way.
More trials run by University Medical Center GroningenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: randomized, placebo-controlled, double-blind, parallel group, multicenter study
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03200860
Sponsor's protocol ID: 2017-001679-22
Other IDs: 2017
Acronym: EMPA-RESPONSE
Status last verified: Apr 2024
First submitted: 23 Jun 2017
Last updated: 17 Apr 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 26378978
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.
PubMed 27299675

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
Not yet recruitingPhase 3
Early Discharge With Subcutaneous Furosemide Versus Standard Care in Acute Heart Failure
Heart Failure, Acute Decompensated Heart Failure
Recruiting
CT Stress Myocardial Perfusion, Fractional Flow Reserve and Angiography in Patients With Stable Chest Pain Syndromes
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Recruiting
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Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)

All Heart Failure Acute trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03200860
Acronym / sponsor ID: EMPA-RESPONSE / 2017-001679-22
Conditions: Heart Failure Acute, Heart Failure，Congestive, Heart Failure; With Decompensation
Keywords: heart failure, diuretic response, empagliflozin
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: University Medical Center GroningenUniversity, hospital or other
Study start: 18 Dec 2017 (actual)
Primary completion: 18 Sep 2019 (actual)
Study completion: 18 Sep 2019 (actual)
First posted: 27 Jun 2017 (actual)
Results: Posted 19 Feb 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: randomized, placebo-controlled, double-blind, parallel group, multicenter study

Arm	Type	Receives
Empagliflozin	Active comparator	Drug: Empagliflozin 10 MGEmpagliflozin 10 mg daily, oral, 30 days
Placebo	Placebo comparator	Drug: Placebo Oral TabletMatching Placebo 10 mg daily, oral, 30 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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:
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

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Empagliflozin 10 MG10 mg daily, oral, 30 days	Drug	Empagliflozin
Placebo Oral TabletMatching Placebo, 10 mg daily, oral, 30 days	Drug	Placebo

Primary outcome

Dyspnea
Time frame: From baseline to Day 4
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
Time frame: Total weight change from baseline to Day 4
Weight change from baseline per 40 mg of Furosemide equivalent
Length of Stay
Time frame: within 60 days
Hospital stay of Index admission
Plasma NTproBNP
Time frame: From baseline to Day 4
Change in NTproBNP

3 secondary outcomes

Death and/or Heart Failure Re-admission
Time frame: Day 30
Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60
Time frame: 60 days
All Cause Mortality
Time frame: 60 day

Results and safety

Results posted to the registry on 19 Feb 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Empagliflozin	41	40
Placebo	39	39

Primary outcome: Dyspnea

Time frame: From baseline to Day 4. Mean (Standard Deviation). Unit: mmxh

Measure	Empagliflozin n = 37	Placebo n = 36
Value	1264 (1211)	1650 (1240)

Empagliflozin vs Placebo: p = 0.18, t-test, 2 sided

Primary outcome: Diuretic Response

Time frame: Total weight change from baseline to Day 4. Mean (Standard Deviation). Unit: kg/40 mg Furosemide equivalent at day 4

Measure	Empagliflozin n = 36	Placebo n = 37
Value	-0.35 (0.44)	-0.12 (1.52)

Empagliflozin vs Placebo: p = 0.37, t-test, 2 sided

Primary outcome: Length of Stay

Time frame: within 60 days. Median (Inter-Quartile Range). Unit: days

Measure	Empagliflozin n = 39	Placebo n = 38
Value	8 (6 to 10)	8 (6 to 9)

Empagliflozin vs Placebo: p = 0.58, Wilcoxon (Mann-Whitney)

Primary outcome: Plasma NTproBNP

Time frame: From baseline to Day 4. Mean (Standard Deviation). Unit: % change in NTproBNP at day 4

Measure	Empagliflozin n = 37	Placebo n = 34
Value	-46 (32)	-42 (31)

Empagliflozin vs Placebo: p = 0.63, t-test, 2 sided

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 60 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Empagliflozin	8 of 40 (20%)	29 of 40 (72.5%)	1 of 40
Placebo	10 of 39 (25.6%)	31 of 39 (79.5%)	3 of 39

Limitations and caveats (from the sponsor): * Limited number of patients * Screened many more patients then were included * no standardized protocol for inhospital treatment for HF

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26378978Zinman 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.
Background: PubMed 27299675Wanner 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.
Individual participant dataSharing planned: No

Related trials for Heart Failure Acute

RecruitingPhase 4
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The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Adriaan Voors, Prof. Dr. principal investigator

University Medical Center Groningen

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Empagliflozin 10 MG in people with Heart Failure Acute and Heart Failure，Congestive, run by University Medical Center Groningen at 5 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dyspnea (time frame: From baseline to Day 4). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03200860, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.