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

NCT03200860 | Completed Phase 2 Results DMC

• 1 other identifier: 2017-001679-22
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Keywords

heart failure; diuretic response; empagliflozin

Outcome Measures

Primary Outcomes (4)

• 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

  From baseline to Day 4

• Diuretic Response

  Weight change from baseline per 40 mg of Furosemide equivalent

  Total weight change from baseline to Day 4

• Length of Stay

  Hospital stay of Index admission

  within 60 days

• Plasma NTproBNP

  Change in NTproBNP

  From baseline to Day 4

Secondary Outcomes (3)

• Death and/or Heart Failure Re-admission

  Day 30

• Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60

  60 days

• All Cause Mortality

  60 day

Other Outcomes (1)

• Serious Adverse Events

  60 days

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Empagliflozin 10 mg daily, oral, 30 days

Drug: Empagliflozin 10 MG

Placebo

PLACEBO COMPARATOR

Matching Placebo 10 mg daily, oral, 30 days

Drug: Placebo Oral Tablet

Interventions

Empagliflozin 10 MG DRUG

10 mg daily, oral, 30 days

Empagliflozin

Placebo Oral Tablet DRUG

Matching Placebo, 10 mg daily, oral, 30 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (5)

TREANT Zorggroep

Emmen, Drenthe, Netherlands

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, North Brabant, Netherlands

Location

ISALA Klinieken

Zwolle, Overijssel, Netherlands

Location

Antonius Ziekenhuis

Sneek, Provincie Friesland, Netherlands

Location

University Medical Center Groningen

Groningen, 9700RB, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 26378978 BACKGROUND

• 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.

  PMID: 27299675 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

* Limited number of patients * Screened many more patients then were included * no standardized protocol for inhospital treatment for HF

Results Point of Contact

• Title: Prof. dr. A.A. Voors
• Organization: University Medical Center Groningen - Department of Cardiology

a.a.voors@umcg.nl

0031503616161

Study Officials

• Adriaan Voors, Prof. Dr.

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind, placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, placebo-controlled, double-blind, parallel group, multicenter study

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: June 27, 2017
• Study Start: December 18, 2017
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: April 17, 2024
• Results First Posted: February 19, 2020

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (5)