title: RITZ-5: randomized intravenous TeZosentan (an endothelin-A/B antagonist) for the treatment of pulmonary edema: a prospective, multicenter, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  The objective of this study was to evaluate the addition of intravenous (IV) tezosentan to standard therapy for patients with pulmonary edema.
  
  
  BACKGROUND
  Tezosentan is an IV nonselective endothelin (ET)-1 antagonist that yields favorable hemodynamic effects in patients with acute congestive heart failure (CHF).
  
  
  METHODS
  Pulmonary edema was defined as acute CHF leading to respiratory failure, as evidenced by an oxygen saturation (SO(2)) <90% by pulse oxymeter despite oxygen treatment. All patients received oxygen 8 l/min through a face mask, 3 mg of IV morphine, 80 mg of furosemide, and 1 to 3 mg/h continuous drip isosorbide-dinitrate according to their blood pressure level and were randomized to receive a placebo or tezosentan (50 or 100 mg/h) for up to 24 h.
  
  
  RESULTS
  Eighty-four patients were randomized. The primary end point, the change in SO(2) from baseline to 1 h, was 9.1 +/- 6.3% in the placebo arm versus 7.6 +/- 10% in the tezosentan group (p = NS). The incidence of death, recurrent pulmonary edema, mechanical ventilation, and myocardial infarction during the first 24 h of treatment was 19% in both groups. Reduced baseline SO(2), lower echocardiographic ejection fraction, high baseline mean arterial blood pressure (MAP), and inappropriate vasodilation (MAP reduction at 30 min of <5% or >30%) correlated with worse outcomes. A post-hoc analysis revealed that the outcome of patients who received only 50 mg/h tezosentan was better than patients in the placebo group whereas patients receiving 100 mg/h had the worst outcomes.
  
  
  CONCLUSIONS
  In the present study, tezosentan (an ET-1 antagonist) did not affect the outcome of pulmonary edema, possibly because of the high dose used.
authors.affiliation: Cardiology Division, Assaf-Harofeh Medical Center, Zerifin, Israel. ekaluski@asaf.health.gov.il
authors.forename: Edo
authors.initials: E
authors.lastname: Kaluski
authors.forename: Isaac
authors.initials: I
authors.lastname: Kobrin
authors.forename: Reuven
authors.initials: R
authors.lastname: Zimlichman
authors.forename: Alon
authors.initials: A
authors.lastname: Marmor
authors.forename: Oscar
authors.initials: O
authors.lastname: Krakov
authors.forename: Olga
authors.initials: O
authors.lastname: Milo
authors.forename: Aline
authors.initials: A
authors.lastname: Frey
authors.forename: Shoshana
authors.initials: S
authors.lastname: Kaplan
authors.forename: Rikardo
authors.initials: R
authors.lastname: Krakover
authors.forename: Avi
authors.initials: A
authors.lastname: Caspi
authors.forename: Zvi
authors.initials: Z
authors.lastname: Vered
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
mesh_terms: D004311:Double-Blind Method; D004452:Echocardiography; D065128:Endothelin Receptor Antagonists; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging; D006801:Humans; D007275:Injections, Intravenous; D011446:Prospective Studies; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000209:etiology; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan