Clinical trial NCT03200860: Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure Acute
Heart Failure，Congestive
Heart Failure; With Decompensation
Keywords: heart failure
diuretic response
empagliflozin
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2017-06-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, placebo-controlled, double-blind, parallel group, multicenter study
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Dyspnea
timeFrame: From baseline to Day 4
measure: Diuretic Response
timeFrame: Total weight change from baseline to Day 4
measure: Length of Stay
timeFrame: within 60 days
measure: Plasma NTproBNP
timeFrame: From baseline to Day 4
Secondary outcomes:
measure: Death and/or Heart Failure Re-admission
timeFrame: Day 30
measure: Inhospital Worsening Heart Failure, All Cause Mortality or Heart Failure Readmission at Day 60
timeFrame: 60 days
measure: All Cause Mortality
timeFrame: 60 day
Other outcomes:
measure: Serious Adverse Events
timeFrame: 60 days
Locations:
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
state: Brabant
city: Emmen
country: Netherlands
facility: TREANT Zorggroep
state: Drenthe
city: Sneek
country: Netherlands
facility: Antonius Ziekenhuis
state: Friesland
city: Zwolle
country: Netherlands
facility: ISALA Klinieken
state: Overijssel
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Adriaan Voors, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.