ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03200860
Recruitment Status : Recruiting
First Posted : June 27, 2017
Last Update Posted : January 1, 2019
Sponsor:
Information provided by (Responsible Party):
A.A.Voors, University Medical Center Groningen

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.


Condition or disease Intervention/treatment Phase
Heart Failure Acute Heart Failure,Congestive Heart Failure; With Decompensation Drug: Empagliflozin 10 MG Drug: Placebo Oral Tablet Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized, placebo-controlled, double-blind, parallel group, multicenter study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double blind, placebo controlled
Primary Purpose: Treatment
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)
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Empagliflozin
Empagliflozin 10 mg daily, oral, 30 days
Drug: Empagliflozin 10 MG
10 mg daily, oral, 30 days

Placebo Comparator: Placebo
Matching Placebo 10 mg daily, oral, 30 days
Drug: Placebo Oral Tablet
Matching Placebo, 10 mg daily, oral, 30 days




Primary Outcome Measures :
  1. Dyspnea [ Time Frame: From baseline to Day 4 ]
    Change in Dyspnea on VAS analogue scale (AUC)

  2. Diuretic Response [ Time Frame: Total weight change from baseline to Day 4 ]
    Weight change from baseline per 40 mg of Furosemide equivalent

  3. Length of Stay [ Time Frame: within 60 days ]
    Hospital stay of Index admission

  4. Plasma NTproBNP [ Time Frame: From baseline to Day 4 ]
    Change in NTproBNP


Secondary Outcome Measures :
  1. Death and/or heart failure re-admission [ Time Frame: Day 30 ]
    All Cause Mortality or HF readmission

  2. Change in creatinine [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    in mg/dL or umol/L

  3. Change in eGFR [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    in mL/min/1.73m2

  4. Change in cystatin C [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    in mg/L

  5. Change in BUN [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    in mg/dL

  6. Change in hemoglobin [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    in g/dL

  7. Change in hematocrit [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    in %

  8. Change in albumin [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    g/dL

  9. Change in urinary sodium excretion [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    mmol/L

  10. Change in urinary albumin to creatinine ratio (UACR) [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    mg/g cr

  11. Change in N-acetyl-beta-D-glucosaminase (NAG) [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    U/g Cr

  12. Change in Neutrophil Gelatinase Associated Lipocalin (NGAL) [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    mg/g Cr

  13. Change in Kidney Injury Molecule 1 (KIM-1) [ Time Frame: Day 4 (or discharge if earlier) and Day 30 ]
    ng/gCr


Other Outcome Measures:
  1. Serious adverse events [ Time Frame: 60 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03200860


Contacts
Contact: Kevin Damman, Dr. 0031503616161 k.damman@umcg.nl

Locations
Netherlands
Jeroen Bosch Ziekenhuis Recruiting
Den Bosch, Brabant, Netherlands
Contact: J Van Kuilenburg         
Principal Investigator: J Van Kuilenburg         
TREANT Zorggroep Recruiting
Emmen, Drenthe, Netherlands
Contact: TDJ Smilde, MD,PhD         
Principal Investigator: TDJ Smilde, MD,PhD         
Antonius Ziekenhuis Recruiting
Sneek, Friesland, Netherlands
Contact: HP Swart         
Principal Investigator: HP Swart, MD,PhD         
ISALA Klinieken Recruiting
Zwolle, Overijssel, Netherlands
Contact: A Elvan         
Principal Investigator: A Elvan         
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9700RB
Contact: Kevin Damman, MD,PhD    0031503616161      
Principal Investigator: Kevin Damman, MD,PhD         
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Principal Investigator: Adriaan Voors, Prof. Dr. University Medical Center Groningen

Publications:
Responsible Party: A.A.Voors, Professor, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03200860     History of Changes
Other Study ID Numbers: 2017-001679-22
First Posted: June 27, 2017    Key Record Dates
Last Update Posted: January 1, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by A.A.Voors, University Medical Center Groningen:
heart failure
diuretic response
empagliflozin

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Empagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs