Clinical trial NCT01873859
Conditions: Diabetes Mellitus Lactic Acidosis
Keywords: Lactic acidosis Contrast media Angiography Diabetic Metformin
Sponsor: Shahid Beheshti University of Medical Sciences
Start date: 2013-05-01; Completion date: 2014-02-01
Enrollment: 166 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether metformin causes lactic acidosis in diabetic patients with preserved kidney function, undergoing coronary angiography or angioplasty with new contrast media.

In other words is it necessary to discontinue metformin before these procedures, even when Iodixanol is used as contrast media, which is isosmolar agent and much more safer than urografin which was the main agent in the previous studies that were the base of present guidelines?

Detailed description:
Although metformin is not directly nephrotoxic, it has been postulated that can impair gluconeogenesis from lactate, which may lead to lactate accumulation under circumstances such as acute renal failure. In diabetic patients receiving metformin, this condition can be encountered in the setting of acute renal failure following contrast media administration, during coronary angiography i.e. contrast-induced nephropathy. As a result, it has been a part of routine clinical practice to discontinue metformin before angiography to prevent metformin-associated lactic acidosis (MALA). However, there is no general consensus regarding the incidence of MALA and evidence for such intervention is poor. On the other hand, discontinuation of metformin can be associated with detrimental effects on glycemic control and thereby may increase cardiovascular risk in diabetic patients undergoing percutaneous coronary interventions. Consequently, questions have been raised recently regarding the routine discontinuation of metformin, in low-risk patients undergoing coronary angiography.

The present study was designed to assess the role of metformin in lactate production in a group of diabetic patients with normal renal function; and to address the questions about significance of routine discontinuation of metformin in low risk patients undergoing coronary angiography.

Iodixanol will be the only contrast media in all patients, because of its low nephrotoxicity. Serum blood urea nitrogen and creatinin; as well as arterial blood gases will be evaluated prior to angiography, and repeated 24 and 48 hours after the procedure. Glomerular filtration rate (GFR) is calculated using Cockcroft-Gault formula {GFR= 0.85 (for women)}.

Contrast-induced acute kidney injury is defined as a 25-50% or 0.3-0.5 mg/dl net increase in creatinine concentration compared to the baseline values. Metformin-associated lactic acidosis (MALA) is defined as an arterial pH (potential of hydrogen)\<7.35 and plasma lactate concentration \>5 mmol⁄L. In the M (-) group metformin will re-started 48 hours after angiography, albeit in the absence of evidence of lactic acidosis and GFR of \>60 mL/min per 1.73 m2.

A written informed consent is taken from all participants and institutional review board has already approved the trial.

Arms: arm 1: Diabetic patients receiving contrast media without discontinuing metformin. arm 2: Diabetic patients receiving contrast media with discontinuation of metformin.
Interventions: intervention 1: Metformin
Intervention descriptions: intervention 1: Incidence of lactic acidosis in diabetic patients receiving contrast media in the presence of metformin.

Protocol documents: