Analysing the Effect of Empagliflozin on Reduction of Tissue Sodium Content in Patients With Chronic Heart Failure

NCT03128528 | Completed Phase 2

• 1 other identifier: CRC2017ELSI
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis is that the SGLT-2 inhibitor empagliflozin reduces tissue sodium content in patients with chronic heart failure, and if the hypothesis is proven, that this mechanism contributes to the beneficial effects found in EMPA-REG Outcome trial potentially via exerting beneficial effects on the vascular structure and function of the micro- and macrocirculation.

Conditions

Chronic Heart Failure

Keywords

SGLT-2 inhibitor, Chronic heart failure, tissue sodium,

Outcome Measures

Primary Outcomes (1)

• Skin sodium content

  Skin sodium content (23Na-MRI) assessed at the lower leg

  14 weeks

Secondary Outcomes (13)

• Muscle sodium content

  14 weeks

• Water content of skin and muscle

  14 weeks

• Sodium excretion

  14 weeks

• 24-hour urine sodium excretion

  14 weeks

• Vascular stiffness Parameter (central systolic pressure)

  14 weeks

Study Arms (2)

Placebo Oral Tablet

PLACEBO COMPARATOR

Patients will be randomized to empagliflozin 10 mg orally once daily or one placebo tablet orally once daily.

Drug: Placebo Oral Tablet

Empagliflozin

ACTIVE COMPARATOR

Patients will be randomized to empagliflozin 10 mg orally once daily or one placebo tablet orally once daily.

Drug: Empagliflozin 10mg

Interventions

Empagliflozin 10mg DRUG

Each patient, after the run-in/wash-out phase, will be randomly assigned in a doubleblind fashion to one of the two treatment sequences according to a randomisation list. and provided by the sponsor.

Also known as: EMPA

Empagliflozin

Placebo Oral Tablet DRUG

Each patient, after the run-in/wash-out phase, will be randomly assigned in a doubleblind fashion to one of the two treatment sequences according to a randomisation list. and provided by the sponsor.

Also known as: PLACEBO

Placebo Oral Tablet

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18 - 85 years
• Male and Female patients (females of child bearing potential must be using adequate contraceptive precautions)
• CHF (symptoms and/or sign of CHF, ejection fraction \< 40% (HfrEF) 14 or symptoms and/or signs of CHF, ejection fraction 40-49 % and NT-pro BNP \> 125 pg/ml, and at least one structural abnormality of left atrium or ventricle (HFmEF) 14 in stable conditions.
• Females of childbearing potential or within two years of the menopause must have a negative urine pregnancy test at screening visit.
• Informed consent has to be given in written form.

You may not qualify if:

• Any other form of diabetes mellitus than type 2 diabetes mellitus
• Use of insulin or any SGLT-2 inhibitor within the past 10 weeks prior to the screening visit (visit 1).
• Patients with more than two blood glucose lowering medications
• Uncontrolled diabetes (fasting plasma glucose ≥ 240 mg/dl, HbA1c ≥ 10%)
• Chronic heart failure NYHA stage IV
• Use of loop diuretics above furosemide \> 80 mg/day, or torasemide \>40 mg/day, or piretanide \> 6 mg/day
• Implanted pacemakers or defibrillators
• Any other relevant clinical contraindication of MRI examination
• Uncontrolled arterial hypertension (i.e. ≥ 180/110 mmHg)
• Severe disorders of the gastrointestinal tract or other diseases which interfere with the pharmacodynamics and pharmacokinetics of study drugs
• Significant laboratory abnormalities such as Serum Glutamate-Oxaloacetate-Transaminase (SGOT) or Serum Glutamate-Pyruvate-Transaminase (SGPT) levels more than 3 x above the upper limit of normal range

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg

Erlangen, 91054, Germany

Location

Related Publications (4)

• Striepe K, Jumar A, Ott C, Karg MV, Schneider MP, Kannenkeril D, Schmieder RE. Effects of the Selective Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin on Vascular Function and Central Hemodynamics in Patients With Type 2 Diabetes Mellitus. Circulation. 2017 Sep 19;136(12):1167-1169. doi: 10.1161/CIRCULATIONAHA.117.029529. No abstract available.

  PMID: 28923906 BACKGROUND

• Bytyqi V, Kannenkeril D, Kolwelter J, Linz P, Bosch A, Striepe K, Karg MV, Nagel AM, Uder M, Schiffer M, Achenbach S, Schmieder RE. Short- and mid-term effects of empagliflozin on sodium balance and fluid regulation in chronic heart failure. Eur J Heart Fail. 2025 Nov 4. doi: 10.1002/ejhf.70078. Online ahead of print.

  PMID: 41186108 DERIVED

• Kolwelter J, Kannenkeril D, Linz P, Jung S, Nagel AM, Bosch A, Ott C, Bramlage P, Noh L, Schiffer M, Uder M, Achenbach S, Schmieder RE. The SGLT2 inhibitor empagliflozin reduces tissue sodium content in patients with chronic heart failure: results from a placebo-controlled randomised trial. Clin Res Cardiol. 2023 Jan;112(1):134-144. doi: 10.1007/s00392-022-02119-7. Epub 2022 Oct 26.

  PMID: 36289063 DERIVED

• Pietschner R, Kolwelter J, Bosch A, Striepe K, Jung S, Kannenkeril D, Ott C, Schiffer M, Achenbach S, Schmieder RE. Effect of empagliflozin on ketone bodies in patients with stable chronic heart failure. Cardiovasc Diabetol. 2021 Nov 9;20(1):219. doi: 10.1186/s12933-021-01410-7.

  PMID: 34753480 DERIVED

MeSH Terms

Interventions

empagliflozin

Study Officials

• Roland E Schmieder, Prof. Dr.

  Universitätsklinikum Erlangen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II, randomized (2:1), prospective, double-blind, placebo controlled, parallel-group, single center study.

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: April 25, 2017
• Study Start: July 1, 2017
• Primary Completion: January 31, 2020
• Study Completion: April 30, 2020
• Last Updated: September 28, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)