SGLT2 Inhibitors in Patients With ADHF During Ventilator Weaning

Ventilator Lung Clinical Trial

Official title:

The Potential Beneficial Effects of SGLT2 Inhibitors in Patients With Acute Decompensated Heart Failure During Ventilator Weaning: a Prospective Multicenter Cohort Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06142474
• Other study ID #: 202209061MINA
• Status: Recruiting
• Phase: Phase 3
• Start date: October 10, 2022
• Est. completion date: October 9, 2030

Study information

• Verified date: October 2023
• Source: National Taiwan University Hospital
• Contact: Chih Fan Yeh
• Phone: 0972652306
• Email: nicholas.yeh[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will explore the potential benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in preventing cardiac ischemia and cardiopulmonary edema in patients with acute decompensated heart failure during weaning from ventilators.

Description:

Patients with acute decompensated HF will be open-label randomly assigned to be treated with or without SGLT2 inhibitors (either empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily) 3 days before ventilator weaning in a ratio of 2:1. If the patients are allocated to SGLT2i treatment group, they will be further randomized equally to either empagliflozin- or dapagliflozin-treated group. A series of examination will be performed to detect weaning-induced cardiac ischemia and weaning-induced cardiopulmonary edema, including electrocardiography, chest X-ray, echocardiography, and biomarkers. Echocardiography Transthoracic echocardiography (TTE) will be performed by a trained operator at several time points: (1) before SBT and SGLT2i initiation; (2) during SBT trial just after initiating SGLT2 inhibitor; (3) during SBT trial 3 days after initiation of SGLT2 inhibitor; (4) within 24 hrs after extubation; (5) 7-10 days after extubation; (6) 90±7 days after extubation. Biomarkers NT-proBNP, plasma protein, high-sensitive cardiac troponin T, and hemoglobin level will be checked at several time points: (1) before spontaneous breathing trial (SBT), (2) during SBT trial (at least 10 mins after the initiation of SBT) just after initiating SGLT2 inhibitor; (3) during SBT (at least 10 mins after the initiation of SBT) trial 3 days after SGLT2 inhibitor; (4) within 24 hrs after extubation; (5) 7~10 days after extubation; (5) 90±7 days after extubation. We will also check arterial blood gas analyses at the end of SBT trial just after initiating SGLT2 inhibitor and 3 days after SGLT2 inhibitor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: October 9, 2030
• Est. primary completion date: October 9, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Patients aged =20 years

2. Currently hospitalized for the primary diagnosis of acute HF (de novo or decompensated chronic HF) in HFrEF patients (LVEF=40%)

3. Meet the stabilization criteria:

A. Systolic BP =100mm Hg and no symptoms of hypotension in the preceding 6 hours B. No increase in i.v. diuretic dose for 6 hours prior to randomization C. No i.v. vasodilators including nitrates within the last 6 hours prior to randomization D. No i.v. inotropic drugs for 24 hours prior to randomization

4. Elevated N-terminal proB-type natriuretic peptide (NT-proBNP) or BNP:

A. Without atrial fibrillation (AF): NT-proBNP =1600 pg/mL or BNP =400 pg/mL B. With AF: NT-proBNP =2400 pg/mL or BNP =600 pg/mL

5. Patients were intubated for at least 24 hour with ventilator settings allowing to initiate the weaning process [SpO2 > 90% or PaO2/FiO2 = 150 mmHg with a fraction of inspired oxygen (FiO2) = 40% and a positive end-expiratory pressure (PEEP) = 8 cmH2O].

Exclusion Criteria:

1. Decision to withdraw life support

2. Cardiogenic shock

3. Hospitalization for HF (HHF) triggered by acute myocardial infarction (AMI) or pulmonary embolism

4. Planned or previous (within 30 days) cardiovascular revascularization or major cardiac surgery/intervention/device implantation

5. Prior acute coronary syndrome, AMI, stroke or transient ischemic accident within 90 days

6. Estimated glomerular filtration rate (eGFR) of less than 30 ml per minute per 1.73 m2 of body-surface area

7. Type 1 diabetes mellitus

8. Poorly controlled type 2 diabetes mellitus (a glycated hemoglobin level above 10.5%)

9. Uncontrolled urinary tract infection

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure Acute
• Ventilator Lung

Intervention

Drug:
• SGLT2 inhibitor
Patients with acute decompensated HF will be open-label randomly assigned to be treated with or without SGLT2 inhibitors (either empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily) 3 days before ventilator weaning in a ratio of 2:1. If the patients are allocated to SGLT2i treatment group, they will be further randomized equally to either empagliflozin- or dapagliflozin-treated group

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (5)

Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Pina IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Oct 14;385(16):1451-1461. doi: 10.1056/NEJMoa2107038. Epub 2021 Aug 27. — View Citation

Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1. Erratum In: J Am Coll Cardiol. 2023 Apr 18;81(15):1551. — View Citation

McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19. — View Citation

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Shah SJ, Desai AS, Jhund PS, Belohlavek J, Chiang CE, Borleffs CJW, Comin-Colet J, Dobreanu D, Drozdz J, Fang JC, Alcocer-Gamba MA, Al Habeeb W, Han Y, Cabrera Honorio JW, Janssens SP, Katova T, Kitakaze M, Merkely B, O'Meara E, Saraiva JFK, Tereshchenko SN, Thierer J, Vaduganathan M, Vardeny O, Verma S, Pham VN, Wilderang U, Zaozerska N, Bachus E, Lindholm D, Petersson M, Langkilde AM; DELIVER Trial Committees and Investigators. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022 Sep 22;387(12):1089-1098. doi: 10.1056/NEJMoa2206286. Epub 2022 Aug 27. — View Citation

Spertus JA, Birmingham MC, Nassif M, Damaraju CV, Abbate A, Butler J, Lanfear DE, Lingvay I, Kosiborod MN, Januzzi JL. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nat Med. 2022 Apr;28(4):809-813. doi: 10.1038/s41591-022-01703-8. Epub 2022 Feb 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety parameters	Markers of volume depletion, hypotension and acute renal failure	30 days
Primary	Composite of weaning failure, recurrent pulmonary edema, and cardiovascular/non-cardiovascular mortality.	Weaning failure is defined that patient is reintubated within 7 days following extubation, irrespective of the use of noninvasive ventilation	90 days
Secondary	Components of the primary endpoint	Weaning failure, recurrent pulmonary edema, and cardiovascular/non-cardiovascular mortality.	90 days
Secondary	Diuretic response	Any poor response to diuretics	after 15 and 30 days of treatment
Secondary	Change in NT-proBNP level	Difference between 30 days and baseline	over 30 days of treatment
Secondary	Occurrence of chronic dialysis or renal transplant or significant, sustained reduction of estimated glomerular filtration rate	Dialysis, renal transplant and eGFR	90 days
Secondary	The therapeutic effect by different SGLT2i on components of the primary endpoint.	Empagliflozin vs Dapagliflozin	90 days