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

Heart Failure,Congestive Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03200860
• Other study ID #: 2017-001679-22
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2017
• Est. completion date: September 18, 2019

Study information

• Verified date: April 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 18, 2019
• Est. primary completion date: September 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Empagliflozin 10 MG
10 mg daily, oral, 30 days
• Placebo Oral Tablet
Matching Placebo, 10 mg daily, oral, 30 days

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch	Brabant
Netherlands	TREANT Zorggroep	Emmen	Drenthe
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Antonius Ziekenhuis	Sneek	Friesland
Netherlands	ISALA Klinieken	Zwolle	Overijssel

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serious Adverse Events	SAE including all cause mortality. Per request Clintrials.gov different from Protocol definition	60 days
Primary	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
Primary	Diuretic Response	Weight change from baseline per 40 mg of Furosemide equivalent	Total weight change from baseline to Day 4
Primary	Length of Stay	Hospital stay of Index admission	within 60 days
Primary	Plasma NTproBNP	Change in NTproBNP	From baseline to Day 4
Secondary	Death and/or Heart Failure Re-admission	Death and/or heart failure re-admission at day 30	Day 30
Secondary	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	60 days
Secondary	All Cause Mortality	All Cause Mortality at 60 days	60 day