RITZ-5: randomized intravenous TeZosentan (an endothelin-A/B antagonist) for the
treatment of pulmonary edema: a prospective, multicenter, double-blind,
placebo-controlled study.
Author(s): Kaluski E(1), Kobrin I, Zimlichman R, Marmor A, Krakov O, Milo O, Frey A, Kaplan
S, Krakover R, Caspi A, Vered Z, Cotter G.
Affiliation(s): Author information:
(1)Cardiology Division, Assaf-Harofeh Medical Center, Zerifin, Israel.
ekaluski@asaf.health.gov.il
Publication date & source: 2003, J Am Coll Cardiol. , 41(2):204-10
OBJECTIVES: 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.
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