Clinical trial NCT01873859: Safety of Continuing Metformin in Diabetic Patients With Normal Kidney Function Receiving Contrast Media
Official title: Incidence of Lactic Acidosis After Coronary Angiography and Angioplasty in Diabetic Patients on Continued Metformin Therapy With Normal Renal Function.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Lactic Acidosis
Keywords: Lactic acidosis
Contrast media
Angiography
Diabetic
Metformin
Lead sponsor: Shahid Beheshti University of Medical Sciences
Sponsor class: OTHER
First posted: 2013-06-10
Enrollment: 166
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* Diabetic patients receiving metformin who were scheduled for:

  * coronary angiography
  * coronary angioplasty

Exclusion Criteria:

* Patients who had contraindication for metformin administration, such as:

  * decompensated heart failure
  * severe liver disease
  * severe hypoxemia
  * GFR\<60 mL/min per 1.73 m2

Primary outcomes:
measure: Incidence of Lactic Acidosis
timeFrame: 48 hrs
measure: Change of Baseline Creatinine 48 hr After Recieving Contrast Media in the Presence or Absence of Metformin Use.
timeFrame: 48 hours from the baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Cardiovascular research center, Modarres hospital.
Study officials:
affiliation: Cardiovascular research center, Modarres hospital, Shahid Beheshti University of Medical Sciences
name: Saeed Alipour Parsa
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goergen SK, Rumbold G, Compton G, Harris C. Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology. 2010 Jan;254(1):261-9. doi: 10.1148/radiol.09090690.