title: Intracoronary local paclitaxel delivery by X-ray contrast media for in-stent restenosis: a clinical pilot study to assess safety and tolerability.
abstract: OBJECTIVE
  Non-stent-based immediate release formulations of paclitaxel have been shown to reduce in-stent restenosis in animal experiments and clinical trials. In the porcine overstretch model paclitaxel dissolved in the contrast medium iopromide inhibited neointimal proliferation in a dose-dependent manner after intracoronary injection and was well tolerated.
  
  
  METHODS
  As a first step entering clinical development, a phase I trial was performed using four ascending paclitaxel dose/concentration levels: samples of up to 100 mL of the contrast medium (iopromide) containing 10, 50, 100 or 200 µM paclitaxel or iopromide (controls) were randomly administered to patients assigned to bare metal stent implantation for single de novo coronary artery lesions. Safety variables, tolerability and angiographic parameters were assessed.
  
  
  RESULTS
  Adverse events, ECG, systolic and diastolic blood pressure, left ventricular ejection fraction, leukocyte count, other hematological or clinical chemistry data did not reveal any trend which could be related to the study medication. Short-lasting serum paclitaxel concentrations remained significantly below those known from cancer therapy. Angiographic late lumen loss was 0.72±0.50 mm (N.=7) in controls versus 0.45±0.65 mm (N.=17) in all paclitaxel-treated patients; binary restenosis rate was 5/7(63%) versus 6/17 (35%) and target lesion revascularization rate was 4/8 (50%) versus 4/24 (17%).
  
  
  CONCLUSIONS
  Intracoronary infusion of paclitaxel dissolved in an X-ray contrast medium was well tolerated. The results show restenosis inhibition, but the number of patients examined was too small to demonstrate a statistically significant inhibition.
authors.affiliation: HELIOS Klinikum Emil-von-Behring, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Rutsch
authors.forename: B
authors.initials: B
authors.lastname: Scheller
authors.forename: A C
authors.initials: AC
authors.lastname: Borges
authors.forename: M
authors.initials: M
authors.lastname: Bräutigam
authors.forename: Y
authors.initials: Y
authors.lastname: Clever
authors.forename: B
authors.initials: B
authors.lastname: Cremers
authors.forename: U
authors.initials: U
authors.lastname: Dietz
authors.forename: W
authors.initials: W
authors.lastname: Richter
authors.forename: U
authors.initials: U
authors.lastname: Speck
mesh_terms: D000368:Aged; D000465:Algorithms; D006328:Cardiac Catheterization / Q000379:methods; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003287:Contrast Media / Q000008:administration & dosage*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000628:therapy; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000628:therapy; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006801:Humans; D007269:Injections, Intra-Arterial; D007472:Iohexol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D010865:Pilot Projects; D012008:Recurrence; D015607:Stents / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D003287:Contrast Media; D007472:Iohexol; C038192:iopromide; D017239:Paclitaxel