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The present study aims to evaluate the strict application of the 2018 European Society of Cardiology guidelines on myocardial revascularization, that recommends to check renal function if patients have taken metformin immediately before angiography and withhold metformin if renal function deteriorates.
The aim of this study is to assess the safety of metformin in diabetic patients undergoing coronary angiography in terms of risk of lactic acidosis and to individuate eventual predictors of augmented lactate after coronary angiography.
The study is designed as an open-label (both physician and participant know that metformin will not be discontinued before PCI and in the following 48 hours), prospective, single arm study.
In our historical cohort of diabetic patients taking metformin, we observed a mean value of lactate of 1.2+0.7 mmol/l.
A total of 150 patients will be enrolled. Patients with any deviations from the study protocol will be enrolled in a parallel observational registry.
The study consists of a screening phase, a 30-day observational phase, and an end-of-follow-up visit or phone interview. The total duration of participation in the study for each participant is approximately 30 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin continuation | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Diabetic patients treated with metformin undergoing coronary angiography will not suspend metformin before and after PCI. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Increase in lactate of 20% | Lactate will be measured from a venous sampling at three different time points, before coronary angiography, the day after (not mandatory) and 3 days after coronary angiography | From preprocedural values (same day of the coronary angiography) to 72 hours after coronary angiography |
| Measure | Description | Time Frame |
|---|---|---|
| Contrast-associated acute kidney injury after coronary angiography. | Contrast-associated acute kidney injury was defined according to the KDIGO definition: increase in serum creatinine of 0.3 mg/dl within 48 hours from coronary angiography or >50% within 7 days (if creatinine after 7 days is available) or urine output of <0.5 ml/kg/hour for at least 6 hours | From 0 to 7 days after coronary angiography |
| Measure | Description | Time Frame |
|---|---|---|
| Death | All cause mortality | Within 30 days after the index coronary angiography |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Giulio Stefanini, MD, PhD | Contact | +390282247384 | giulio.stefanini@gmail.com | |
| Mauro Chiarito, MD | Contact | +390282247009 | mauro.chiarito@humanitas.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Humanitas Research Hospital | Recruiting | Rozzano | Milan | 20089 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19797290 | Background | Pfisterer ME, Zellweger MJ. Therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009 Oct 1;361(14):1407; author reply 1409-10. doi: 10.1056/NEJMc091419. No abstract available. | |
| 8569826 | Background | Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996 Feb 29;334(9):574-9. doi: 10.1056/NEJM199602293340906. No abstract available. |
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The data that support the findings of this study will be available from the corresponding author on reasonable request.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 22, 2019 | Feb 18, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 22, 2019 | Feb 18, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D003324 | Coronary Artery Disease |
| D000140 | Acidosis, Lactic |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Metformin associated lactic acidosis | Lactic acidosis was defined as pH less than or equal to 7.35 and lactatemia greater than 2.2 mmol/L | At 24 and 72 hours after coronary angiography |
| 21959259 | Background | Maznyczka A, Myat A, Gershlick A. Discontinuation of metformin in the setting of coronary angiography: clinical uncertainty amongst physicians reflecting a poor evidence base. EuroIntervention. 2012 Jan;7(9):1103-10. doi: 10.4244/EIJV7I9A175. |
| 15808754 | Background | Timmer JR, Ottervanger JP, de Boer MJ, Dambrink JH, Hoorntje JC, Gosselink AT, Suryapranata H, Zijlstra F, van 't Hof AW; Zwolle Myocardial Infarction Study Group. Hyperglycemia is an important predictor of impaired coronary flow before reperfusion therapy in ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2005 Apr 5;45(7):999-1002. doi: 10.1016/j.jacc.2004.12.050. |
| 31553855 | Background | Mehran R, Dangas GD, Weisbord SD. Contrast-Associated Acute Kidney Injury. Reply. N Engl J Med. 2019 Sep 26;381(13):1296-1297. doi: 10.1056/NEJMc1908879. No abstract available. |
| 30667361 | Background | Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO. 2018 ESC/EACTS Guidelines on myocardial revascularization. EuroIntervention. 2019 Feb 20;14(14):1435-1534. doi: 10.4244/EIJY19M01_01. No abstract available. |
| 15338847 | Background | Parra D, Legreid AM, Beckey NP, Reyes S. Metformin monitoring and change in serum creatinine levels in patients undergoing radiologic procedures involving administration of intravenous contrast media. Pharmacotherapy. 2004 Aug;24(8):987-93. doi: 10.1592/phco.24.11.987.36131. |
| 9630271 | Background | Nawaz S, Cleveland T, Gaines PA, Chan P. Clinical risk associated with contrast angiography in metformin treated patients: a clinical review. Clin Radiol. 1998 May;53(5):342-4. doi: 10.1016/s0009-9260(98)80005-6. |
| 17692741 | Background | Laskey WK, Jenkins C, Selzer F, Marroquin OC, Wilensky RL, Glaser R, Cohen HA, Holmes DR Jr; NHLBI Dynamic Registry Investigators. Volume-to-creatinine clearance ratio: a pharmacokinetically based risk factor for prediction of early creatinine increase after percutaneous coronary intervention. J Am Coll Cardiol. 2007 Aug 14;50(7):584-90. doi: 10.1016/j.jacc.2007.03.058. Epub 2007 Jul 30. |
| 36747244 | Derived | Chiarito M, Sanz-Sanchez J, Piccolo R, Condello F, Liccardo G, Maurina M, Avvedimento M, Regazzoli D, Pagnotta P, Garcia-Garcia HM, Mehran R, Federici M, Condorelli G, Diez Gil JL, Reimers B, Ferrante G, Stefanini G. Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial. Cardiovasc Diabetol. 2023 Feb 6;22(1):28. doi: 10.1186/s12933-023-01744-4. |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |