Efficacy of SGLT2 Inhibitors in Adults With Sepsis

NCT06473844 | Recruiting DMC

• 1 other identifier: UW 23-609
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Goal of this clinical trial is to examine the safety and efficacy of SGLT2 inhibitors on the clinical outcomes in patients with sepsis. Main study outcomes are as follows: (i) Primary objective is to examine the efficacy and safety of SGLT2 inhibitors on clinical outcomes in patients with sepsis. (ii) Secondary objective is to examine the effect of SGLT2 inhibitors on inflammatory markers in patients with sepsis.

Conditions

Sepsis; Inflammation; SGLT2 Inhibitors; Critically Ill; Organ Dysfunction Syndrome

Keywords

SGLT2 inhibitors; Sepsis; Inflammatory Markers; Critically Ill; Organ dysfunction

Outcome Measures

Primary Outcomes (2)

• Mortality

  Patient 28-day mortality

  28-day mortality

• Change in Sequential Organ Failure Assessment (SOFA) score

  Score is based on lab results and clinical data. Higher SOFA scores indicate higher risk of ICU mortality. Lower SOFA scores predicts lower risk of ICU mortality.

  Baseline and day 7 score

Secondary Outcomes (1)

• Interleukin-6, Interleukin-1 beta, TNF-a, IFN-gamma, Procalcitonin, C-reactive protein

  Baseline and day 7

Study Arms (2)

SGLT2 inhibitor empagliflozin

EXPERIMENTAL

10mg daily from recruitment to hospital discharge

Drug: Empagliflozin 10 MG

Placebo

PLACEBO COMPARATOR

1 tablet daily from recruitment to hospital discharge

Drug: Placebo

Interventions

Empagliflozin 10 MG DRUG

Empagliflozin 10mg once daily from recruitment to hospital discharge

Also known as: Jardiance

SGLT2 inhibitor empagliflozin

Placebo DRUG

Placebo single tablet once daily from recruitment to hospital discharge

Placebo

Eligibility Criteria

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

You may qualify if:

• Aged 18 years or above
• New onset of sepsis within 48 hours defined according to the Sepsis-3 criteria. (≥2 SOFA)
• Provision of signed and dated informed consent form from participant or surrogate
• Ability to take and adhere to oral and enteral medication regimen
• Willingness to comply

You may not qualify if:

• Current or recent use of SGLT2 inhibitors (within 12wks prior to randomization)
• Impaired renal function
• Clinically unstable or in refractory hypotension
• History of ketoacidosis
• Gastrointestinal surgery or GI absorption / malabsorption disorder
• Pregnancy
• Known allergic or hypersensitivity reactions to any SGLT2 inhibitors
• Treatment with another investigational drug or other interventions within 30 days prior to trial

Sponsors & Collaborators

• Hospital Authority, Hong Kong: lead
• Chinese University of Hong Kong: collaborator

Study Sites (3)

4/F Main Clinical Block and Trauma Centre, Prince of Wales Hospital, Shatin, New Territories, Hong Kong

Hong Kong, Hong Kong, 0000, Hong Kong

NOT YET RECRUITING

Adult Intensive Care Unit, Queen Mary Hospital, 102 Pok Fu Lam Road, Hong Kong

Hong Kong, Hong Kong, 0000, Hong Kong

RECRUITING

The University of Hong Kong

Hong Kong, 00, Hong Kong

RECRUITING

Related Publications (25)

• Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.

  PMID: 31954465 BACKGROUND

• Global report on the epidemiology and burden of sepsis: current evidence, identifying gaps and future directions. Geneva: World Health Organization, 2020. (https://apps.who.int/iris/bitstream/handle/10665/334216/9789240010789-eng.pdf).

  BACKGROUND

• Ling L, Ho CM, Ng PY, Chan KCK, Shum HP, Chan CY, Yeung AWT, Wong WT, Au SY, Leung KHA, Chan JKH, Ching CK, Tam OY, Tsang HH, Liong T, Law KI, Dharmangadan M, So D, Chow FL, Chan WM, Lam KN, Chan KM, Mok OF, To MY, Yau SY, Chan C, Lei E, Joynt GM. Characteristics and outcomes of patients admitted to adult intensive care units in Hong Kong: a population retrospective cohort study from 2008 to 2018. J Intensive Care. 2021 Jan 6;9(1):2. doi: 10.1186/s40560-020-00513-9.

  PMID: 33407925 BACKGROUND

• Centre for Health Protection DoH, The Government of the Hong Kong Special Administrative Region. Death Rates by Leading Causes of Death, 2001 - 2021. (https://www.chp.gov.hk/en/statistics/data/10/27/117.html).

  BACKGROUND

• Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R, Billot L, Correa M, Glass P, Harward M, Joyce C, Li Q, McArthur C, Perner A, Rhodes A, Thompson K, Webb S, Myburgh J; ADRENAL Trial Investigators and the Australian-New Zealand Intensive Care Society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):797-808. doi: 10.1056/NEJMoa1705835. Epub 2018 Jan 19.

  PMID: 29347874 BACKGROUND

• Lamontagne F, Masse MH, Menard J, Sprague S, Pinto R, Heyland DK, Cook DJ, Battista MC, Day AG, Guyatt GH, Kanji S, Parke R, McGuinness SP, Tirupakuzhi Vijayaraghavan BK, Annane D, Cohen D, Arabi YM, Bolduc B, Marinoff N, Rochwerg B, Millen T, Meade MO, Hand L, Watpool I, Porteous R, Young PJ, D'Aragon F, Belley-Cote EP, Carbonneau E, Clarke F, Maslove DM, Hunt M, Chasse M, Lebrasseur M, Lauzier F, Mehta S, Quiroz-Martinez H, Rewa OG, Charbonney E, Seely AJE, Kutsogiannis DJ, LeBlanc R, Mekontso-Dessap A, Mele TS, Turgeon AF, Wood G, Kohli SS, Shahin J, Twardowski P, Adhikari NKJ; LOVIT Investigators and the Canadian Critical Care Trials Group. Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit. N Engl J Med. 2022 Jun 23;386(25):2387-2398. doi: 10.1056/NEJMoa2200644. Epub 2022 Jun 15.

  PMID: 35704292 BACKGROUND

• Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.

  PMID: 11794169 BACKGROUND

• Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022 Nov 19;400(10365):1788-1801. doi: 10.1016/S0140-6736(22)02074-8. Epub 2022 Nov 6.

  PMID: 36351458 BACKGROUND

• 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

• Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.

  PMID: 28605608 BACKGROUND

• Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28.

  PMID: 32865377 BACKGROUND

• Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis K, Tousoulis D. The impact of SGLT2 inhibitors on inflammation: A systematic review and meta-analysis of studies in rodents. Int Immunopharmacol. 2022 Oct;111:109080. doi: 10.1016/j.intimp.2022.109080. Epub 2022 Jul 28.

  PMID: 35908505 BACKGROUND

• Lee N, Heo YJ, Choi SE, Jeon JY, Han SJ, Kim DJ, Kang Y, Lee KW, Kim HJ. Anti-inflammatory Effects of Empagliflozin and Gemigliptin on LPS-Stimulated Macrophage via the IKK/NF-kappaB, MKK7/JNK, and JAK2/STAT1 Signalling Pathways. J Immunol Res. 2021 Jun 2;2021:9944880. doi: 10.1155/2021/9944880. eCollection 2021.

  PMID: 34124273 BACKGROUND

• Li N, Chen J, Wang P, Fan H, Hou S, Gong Y. Major signaling pathways and key mediators of macrophages in acute kidney injury (Review). Mol Med Rep. 2021 Jun;23(6):455. doi: 10.3892/mmr.2021.12094. Epub 2021 Apr 21.

  PMID: 33880578 BACKGROUND

• Wu MZ, Chandramouli C, Wong PF, Chan YH, Li HL, Yu SY, Tse YK, Ren QW, Yu SY, Tse HF, Lam CSP, Yiu KH. Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors. Diabetes Metab. 2022 Nov;48(6):101367. doi: 10.1016/j.diabet.2022.101367. Epub 2022 Jun 23.

  PMID: 35753654 BACKGROUND

• Ng PY, Ng AK, Ip A, Wu MZ, Guo R, Yiu KH. Risk of ICU Admission and Related Mortality in Patients With Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors: A Territory-Wide Retrospective Cohort Study. Crit Care Med. 2023 Aug 1;51(8):1074-1085. doi: 10.1097/CCM.0000000000005869. Epub 2023 Apr 7.

  PMID: 37026864 BACKGROUND

• Vaduganathan M, Claggett BL, Jhund P, de Boer RA, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Shah SJ, Desai AS, Hegde SM, Lindholm D, Petersson M, Langkilde AM, McMurray JJV, Solomon SD. Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial. JAMA Cardiol. 2022 Dec 1;7(12):1259-1263. doi: 10.1001/jamacardio.2022.3750.

  PMID: 36190011 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

• Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. No abstract available.

  PMID: 8844239 BACKGROUND

• Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.

  PMID: 19414839 BACKGROUND

• Ostadal P, Rokyta R, Karasek J, Kruger A, Vondrakova D, Janotka M, Naar J, Smalcova J, Hubatova M, Hromadka M, Volovar S, Seyfrydova M, Jarkovsky J, Svoboda M, Linhart A, Belohlavek J; ECMO-CS Investigators. Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock: Results of the ECMO-CS Randomized Clinical Trial. Circulation. 2023 Feb 7;147(6):454-464. doi: 10.1161/CIRCULATIONAHA.122.062949. Epub 2022 Nov 6.

  PMID: 36335478 BACKGROUND

• 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.

  PMID: 36027570 BACKGROUND

• Karakike E, Kyriazopoulou E, Tsangaris I, Routsi C, Vincent JL, Giamarellos-Bourboulis EJ. The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort. Crit Care. 2019 Nov 29;23(1):387. doi: 10.1186/s13054-019-2665-5.

  PMID: 31783881 BACKGROUND

• Ling L, Chen Z, Lui G, Wong CK, Wong WT, Ng RWY, Tso EYK, Fung KSC, Chan V, Yeung ACM, Hui DSC, Chan PKS. Longitudinal Cytokine Profile in Patients With Mild to Critical COVID-19. Front Immunol. 2021 Dec 6;12:763292. doi: 10.3389/fimmu.2021.763292. eCollection 2021.

  PMID: 34938289 BACKGROUND

• Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients. Crit Care Med. 2006 May;34(5):1297-310. doi: 10.1097/01.CCM.0000215112.84523.F0.

  PMID: 16540951 BACKGROUND

MeSH Terms

Conditions

Sepsis; Inflammation; Critical Illness

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Central Study Contacts

Pauline Yeung Ng, MBBS, FHKCP

CONTACT

39103372; pyeungng@hku.hk

Calvin Tam, BSN, RN

CONTACT

07783323202; ct7331@hku.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: June 25, 2024
• Study Start: March 5, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: March 19, 2025

Record last verified: 2024-10

Locations

HK (3)