CLINICAL STUDY: CARDIAC ARREST AND PULMONARY EDEMA
RITZ-5: randomized intravenousTeZosentan (an endothelin-A/B antagonist)for the treatment of pulmonary edema
A prospective, multicenter, double-blind, placebo-controlled study
Edo Kaluski, MD, FACC*,*,
Isaac Kobrin, MD||,
Reuven Zimlichman, MD ,
Alon Marmor, MD ,
Oscar Krakov, MD ,
Olga Milo, MD*,
Aline Frey, PharmD||,
Shoshana Kaplan, MD*,
Rikardo Krakover, MD*,
Avi Caspi, MD||,
Zvi Vered, MD, FACC*,
Gad Cotter, MD* RITZ-5 Investigators
* Cardiology Division, Assaf-Harofeh Medical Center, Zerifin, Israel
Department of Medicine-Edith Wolfson Medical Center, Holon, Israel
Cardiology DepartmentRivka Ziv Medical Center, Safad, Israel
Cardiology DivisionKaplan Medical Center, Rehovot, Israel
|| Actelion Ltd., Allschwil, Switzerland
Manuscript received May 7, 2002;
revised manuscript received August 13, 2002,
accepted September 6, 2002.
* Reprint requests and correspondence: Dr. Edo Kaluski, Director of Coronary Care Unit, Assaf Harofeh Medical Center, Zerifin, DN Beer Yacov, 70300 Israel. ekaluski{at}asaf.health.gov.il
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 (SO2) <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 SO2 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 SO2, 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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Abbreviations and Acronyms
| | CHF | | congestive heart failure | | EF | | ejection fraction | | ET | | endothelin | | IV | | intravenous | | MAP | | mean arterial blood pressure | | MI | | myocardial infarction | | RITZ | | Randomized Intravenous TeZosentan | | SO2 | | oxygen saturation |
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