Metformin in Diabetic Patients Undergoing Coronary Angiography

Coronary Artery Disease Clinical Trial

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Official title:

Metformin Continuation Safety in Diabetic Patients Undergoing Coronary Angiography

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04766008
• Other study ID #: 20190918
• Status: Recruiting
• Phase: Phase 4
• Start date: January 15, 2020
• Est. completion date: April 30, 2022

Study information

• Verified date: April 2022
• Source: Humanitas Hospital, Italy
• Contact: Giulio Stefanini, MD, PhD
• Phone: +390282247384
• Email: giulio.stefanini[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: April 30, 2022
• Est. primary completion date: April 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diabetic patients treated with metformin undergoing coronary angiography.

Exclusion Criteria:

• Known coronary anatomy with planned complex percutaneous coronary intervention with high probability of large amount of contrast use (3.7 * estimated glomerular filtration rate; e.g.: 167 ml in a patients with an eGFR of 45 ml/min/1.73m2).

• Moderate to severe impairment of renal function (eGFR<45 ml/min).

• Moderate to severe impairment of liver function (Child-Pugh class B or C).

• Severely impaired left ventricular ejection fraction (LVEF <35%).

• Patients undergoing primary percutaneous coronary intervention (i.e., patients presenting with ST elevation myocardial infarction).

• Severe to very severe chronic obstructive pulmonary disease (GOLD class 3 to 4).

• Patients scheduled for cardiac surgery in the following 5 days.

• Inability to provide informed consent.

Related Conditions & MeSH terms

• Acidosis
• Acidosis, Lactic
• Contrast-induced Nephropathy
• Coronary Artery Disease
• Diabetes Mellitus
• Lactic Acidosis With Diabetes Mellitus
• Metformin Associated Lactic Acidosis

Intervention

Drug:
• Metformin
Diabetic patients treated with metformin undergoing coronary angiography will not suspend metformin before and after PCI.

Locations

Country	Name	City	State
Italy	Humanitas Research Hospital	Rozzano	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Humanitas Hospital, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996 Feb 29;334(9):574-9. Review. — View Citation

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. Epub 2007 Jul 30. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Jüni 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. — View Citation

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. Erratum in: Pharmacotherapy. 2004 Oct;24(10):1489. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Death	All cause mortality	Within 30 days after the index coronary angiography
Primary	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
Secondary	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
Secondary	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

External Links

•   Book on the principles and practice of sample size calculation for clinical trials (with details on design, analysis, and interpretation of data from clinical trials)