SGLT-2 Inhibitors in Prevention of Post-procedural Renal and Cardiovascular Complications aFter PCI Among Patients With Diabetes Mellitus and Coronary Artery Disease: a Prospective, Randomized, Pilot Study (SAFE-PCI)

Phase 4

• Conditions: Diabetes Mellitus, Type 2; Coronary Artery Disease; Acute Kidney Injury
• Interventions: Drug: empagliflozin 25 MG

• Registration Number: NCT05037695
• Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary

Patients with type 2 diabetes mellitus (DM) have higher risk of major cardiovascular events (MACE) and renal disfunction. The Sodium-glucose cotransporter-2 inhibitors (iSGLT2) reduces hyperglycemia in patients with type 2 DM and have multiple metabolic effects, lowering primary composite cardiovascular outcomes and progression to renal failure. 25% of patients with Stable Ischemic Heart Disease (SIHD) undergoing PCI are diabetics being one of the most prevalent and important risk factors for the development of contrast induced nephropathy (CIN). The occurence of CIN is associated with higher rates of death, loss of renal function, necessity of dialysis and increase of health care costs. In this pilot study we sought to evaluate if the iSGLT2 would prevent periprocedural complications - such as periprocedural CIN and MI - in type 2 DM patients undergoing PCI through the assessment of renal and myocardial biomarkers

Detailed Description

* Prospective, unblinded, randomized (1:1), single-center pilot study of 40 patients allocated to one of the treatment arms (OMT + empaglifozin or OMT). Strategies to reduce Contrast-induced acute kidney injury will be used in both study arms

* The study population will be composed of patients with type II diabetes mellitus and coronary artery disease (CAD) suitable for PCI of one or more coronary vessels

* After discharge, all subjects will be clinically followed-up during hospitalization and for 30 days after PCI.

* Unless contra-indicated, all patients will receive intravenous hydration during 12 hours pre- and 12 hours post-PCI. Saline (NaCl 0.9%) infusion is recommended at a dose of 1 ml / kg body weight per hour and reduced to 0.5 ml/kg/h for those at high risk of volume overload (e.g. reduced left ventricular function or overt heart failure). All nephrotoxic drugs will be suspended at least 24 hours before the procedure.

* Operators will be strongly recommended to follow strict strategies to reduce the total volume of contrast for all patients

* All percutaneous procedures will be performed using non-ionic, low-osmolar or iso-osmolar, iodine-based contrast media

* The study groups will be compared according to the intention-to-treat principle. Categorical variables will be compared by Fisher's exact testing and continuous variables by Student's T testing. Time-dependent events will be estimated by the Kaplan-Meier method and compared by Hazards Cox modeling or log-rank test

Study Timeline

• Study First Submitted: 2021-06-21
• Study Start: 2021-07-21
• Status Verified: 2021-09
• Study First Submitted QC: 2021-09-03
• Last Update Submitted: 2021-09-03
• Study First Posted: 2021-09-08
• Last Update Posted: 2021-09-08
• Primary Completion: 2022-07
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Age ≥ 18 years
• Type II Diabetes mellitus
• Finding of obstructive coronary artery disease (≥50% stenosis in major epicardial vessel) and clinical indication of percutaneous coronary intervention.(PCI)
• Participant is willing to comply with all aspects of the protocol, including adherence to the assigned strategy, medical therapy and follow-up visits
• Participant is willing to give written informed consent

Exclusion Criteria

• Estimated glomerular filtration rate (eGFR) < 30mL/min/1,73m2 or dialysis
• Inability to comply with the protocol
• Urgent need for PCI
• Acute coronary syndrome within the previous 30 days
• Use of iodinated contrast or other nephrotoxic agents < 7 days
• Angina after coronary bypass surgery
• Canadian Cardiovascular Society Class IV angina, including unprovoked rest angina
• Life expectancy less than the duration of the trial due to non-cardiovascular comorbidity
• Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
empagliflozin + OMT	empagliflozin 25 MG	empagliflozin 25mg - Daily - at least 15 days before the PCI procedure OMT - Optimized Medical Therapy - conventional drug therapy with oral antidiabetics and/or insulin plus use of anti-platelet, anti-hypertensive and lipid-lowering agents necessary to obtain adequate values for pressure, lipid control and glycemia, in accordance with international guidelines and protocols. Strategies to reduce Contrast-induced acute kidney injury will be used in both study arms

Primary Outcome Measures

Name	Time	Method
NGAL values in pre-specified periods	Day 30	Delta and area under curve
Serum creatinine values in pre-specified periods	Day 30	Delta and area under curve

Secondary Outcome Measures

Name	Time	Method
Occurrence of definite or probable stent thrombosis	Until 30 days	Stent thrombosis will be defined as the occurrence of definite or probable stent thrombosis according to the Academic Research Consortium (ARC) criteria
Biomarkers elevation ≥10 upper reference limit (URL) for creatine kinase MB (CKMB) and/or ≥70 URL for troponin	24 hours after PCI	Periprocedural MI will be defined as biomarkers elevation ≥10 upper reference limit (URL) for creatine kinase MB (CKMB) and/or ≥70 URL for troponin
Increase in serum creatinine ≥ 0.3 mg/dl or 50% from the baseline value, within 48 hours after the index procedure	48 hours after PCI	CI-AKI will be defined as an increase in serum creatinine ≥ 0.3 mg/dl or 50% from the baseline value, within 48 hours after the index procedure CI-AKI will be defined as an increase in serum creatinine ≥ 0.3 mg/dl or 50% from the baseline value, within 48 hours after the index procedure
Myocardial Infarction	Until 30 days	Secondary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, definite or probable stent thrombosis, stroke, bleeding (BARC 3-5) or death
Death From Cardiovascular Causes	Until 30 days	Secondary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, definite or probable stent thrombosis, stroke, bleeding (BARC 3-5) or death
Stroke	Until 30 days	Secondary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, definite or probable stent thrombosis, stroke, bleeding (BARC 3-5) or death
Hospitalization for Unstable Angina	Until 30 days	Secondary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, definite or probable stent thrombosis, stroke, bleeding (BARC 3-5) or death
Death	Until 30 days	Secondary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, definite or probable stent thrombosis, stroke, bleeding (BARC 3-5) or death
Bleeding (BARC 3-5)	Until 30 days	Secondary Composite Outcome: Death From Cardiovascular Causes, Myocardial Infarction, or Hospitalization for Unstable Angina, definite or probable stent thrombosis, stroke, bleeding (BARC 3-5) or death

Trial Locations

Locations (1)

Instituto do Coracao - HCFMUSP; 🇧🇷 Sao Paulo, Brazil