Tight Glycemic Control During Angioplasty Revascularization Reduces Coronary Stent Restenosis
Condition: Restenosis; Tight Glycemic Control
Study type: Interventional

Summary: 
      A multicentric study will evaluate whether peri-procedural tight glycemic control during
      angioplasty revascularization for acute coronary syndrome (ACS) reduces circulating
      inflammatory cytokines and thrombus formation in hyperglycaemic patients. Moreover, the
      investigators will assess whether the tight glycemic control during the first month from
      coronary event reduces the incidence of coronary stent restenosis at 6-months from PCI.
    

Detailed description: 
      The study design will be structured on the basis of protocol Yale. Upon emergency wards
      admission, all patients will be assigned to undergo prompt coronary revascularization. After
      PCI procedures, hyperglycemic patients will be randomly assigned to intensive glucose control
      (IGC group) and those treated with conventional glucose control (CGC group). In the patients
      with In the CGC group, continuous insulin infusion of 50 IU Actrapid HM (Novo Nordisk) in 50
      ml NaCl (0.9% using a Perfusor-FM pump) will be started only when blood glucose levels
      exceeded 200 mg/dl and adjusted to keep blood glucose between 180 and 200 mg/dl. When blood
      glucose fell <180 mg/dl, insulin infusion will be tapered and eventually stopped. In the IGC
      group, insulin infusion will be started when blood glucose levels exceeded 140 mg/dl and
      adjusted to maintain glycemia at 80-140 mg/dl. During insulin infusion, oral feeding will be
      stopped and parenteral nutrition (13±5 Kcal/kg-1/day-1) will be started. After the start of
      insulin infusion protocol a glycemic control will be provided every hour in order to obtain
      three consecutive values that were within the goal range. The infusion will be lasted until
      stable glycemic goal (ICG group: 80-140 mg/dl; CGC group: 180-200 mg/dl) at least for 24 h.
      After glycemic goal will be maintained for 24 h, a parenteral nutrition was stopped and
      feeding will be started according to European guidelines. Subcutaneous insulin will be
      initiated at the cessation of the infusion. After discharge from the hospital, insulin will
      be given as short-acting insulin before meals and long-acting insulin in the evening for 30
      days from PCI in both group. In IGC group, the treatment goal will be a fasting blood glucose
      level of 90-140 mg/dl and a non-fasting level of <180 mg/dl. In CGC group, the treatment goal
      will be fasting blood glucose and postprandial levels of <200 mg/dl. With regard to the full
      medical therapy, the protocol stated that the use of concomitant treatment should be as
      uniform as possible and according to evidence-based international guidelines for ACS. After
      30 days from PCI, all patients with established diabetes and newly diagnosed diabetes will be
      managed and followed for 6 month after PCI, as outpatients, to maintain HbA1c <7% and blood
      glucose level of 90-140 mg/dl and a non-fasting level of <180 mg/dl.

      Coronary Angiography Coronary angiograms at baseline, immediately after PCI, and at 6 months
      will be performed in at least 2 orthogonal views after intracoronary nitroglycerin. Minimum
      lumen diameter (MLD) and mean reference diameter (RD), obtained by averaging 5-mm segments
      proximal and distal to the target lesion location, will be used to calculate diameter
      stenosis as follows: (1-MLD/RD)X100. Late loss will the change in MLD from final PCI to
      follow-up. In-stent analysis will be confined to the stent itself, and in-segment analysis
      will be included the stent plus 5-mm segments proximal and distal to the stent. Binary
      restenosis will be defined as a <50% diameter stenosis. Qualitative analysis will be done
      with standard published methods.

      IVUS Imaging and Analysis IVUS at baseline, immediately after PCI, and at 6 months will be
      performed with iLab, Galaxy, and ClearView or In Vision Gold with 20-MHz EagleEye catheters.
      IVUS imaging will be performed with motorized pullback at 0.5 mm/s to include the stent and
      >5 mm segments proximal and distal to the stent. IVUS studies will be archived onto super-VHS
      tape, CD-ROM, or DVD and will be sent to an independent, treatment-allocation- blinded, IVUS
      core laboratory for quantitative and qualitative analyses with validated planimetry software.
      Quantitative analysis will include measurement every 1 mm of the external elastic membrane
      (EEM), stent, and lumen cross-sectional areas (CSAs). Plaque plus media CSA will be
      calculated as EEM minus lumen. Neointimal hyperplasia (NIH) will be calculated as stent minus
      lumen. Once a complete set of CSA measurements will be obtained, intrastent and stent-edge
      volumes (EEM, plaque plus media, stent,lumen, and NIH) will be calculated with Simpson's rule
      and normalized for stent and reference segment length. Percent net volume obstruction will be
      calculated as NIH divided by stent volume.

      Qualitative analysis will include stent malapposition (blood speckle behind stent struts),
      categorized as persistent (visible both at baseline and follow-up), resolved (visible only at
      baseline), and late acquired (only visible at follow-up); intrastent plaque and/or thrombus
      protrusion (IVUS cannot reliably differentiate between plaque and thrombus protruding through
      stent struts); stent fracture (absence of struts over more than one third of the stent
      circumference); aneurysm(lumen >50% larger than the proximal reference); and edge dissection.
    

Intervention name(s): Insulin; Insulin
Intervention type(s): Drug; Drug
Intervention description(s): Insulin infusion will be started when blood glucose levels exceeded 140 mg/dl and adjusted to maintain glycemia at 80-140 mg/dl. During insulin infusion, oral feeding will be stopped and parenteral nutrition (13±5 Kcal/kg-1/day-1) will be started. After the start of insulin infusion protocol a glycemic control will be provided every hour in order to obtain three consecutive values that were within the goal range. The infusion will be lasted until stable glycemic goal (80-140 mg/dl) at least for 24 h. After glycemic goal will be maintained for 24 h, a parenteral nutrition was stopped and feeding will be started according to European guidelines. Subcutaneous insulin will be initiated at the cessation of the infusion. After discharge from the hospital, insulin will be given as short-acting insulin before meals and long-acting insulin in the evening for 30 days from PCI. The treatment goal will be a fasting blood glucose level of 90-140 mg/dl and a non-fasting level of <180 mg/dl.; Continuous insulin infusion of 50 IU Actrapid HM (Novo Nordisk) in 50 ml NaCl (0.9% using a Perfusor-FM pump) will be started only when blood glucose levels exceeded 200 mg/dl and adjusted to keep blood glucose between 180 and 200 mg/dl. When blood glucose fell <180 mg/dl, insulin infusion will be tapered and eventually stopped.The infusion will be lasted until stable glycemic goal (180-200 mg/dl) at least for 24 h. After glycemic goal will be maintained for 24 h, a parenteral nutrition was stopped and feeding will be started according to European guidelines. Subcutaneous insulin will be initiated at the cessation of the infusion. After discharge from the hospital, insulin will be given as short-acting insulin before meals and long-acting insulin in the evening for 30 days from PCI in both group. The treatment goal will be fasting blood glucose and postprandial levels of <200 mg/dl.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: restenosis; insulin; hyperglycemia