A pilot safety trial of prolonged (48 h) infusion of the dual endothelin-receptor
antagonist tezosentan in patients with advanced heart failure.
Author(s): Torre-Amione G(1), Durand JB, Nagueh S, Vooletich MT, Kobrin I, Pratt C.
Affiliation(s): Author information:
(1)Winter Center for Heart Failure Research and the Eugene and Judith Campbell
Laboratories for Cardiac Transplantation Research, Methodist Hospital and Houston
VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA.
gtorre@bcm.tmc.edu
Publication date & source: 2001, Chest. , 120(2):460-6
STUDY OBJECTIVES: Tezosentan, an IV dual endothelin-receptor antagonist, has
demonstrated beneficial hemodynamic effects in patients with advanced heart
failure. In addition, no notable differences in safety and tolerability variables
were detected between tezosentan-treated and placebo-treated patients when
infused over 4 to 6 h. The present study was conducted primarily to assess the
safety and tolerability of tezosentan when administered over a prolonged, 48-h
treatment period, and secondarily to investigate hemodynamic response.
DESIGN: This randomized, double-blind, active-controlled study of continual IV
administration of two dosages of tezosentan (20 mg/h and 50 mg/h; n = 6 each) or
dobutamine (5 microg/kg/min; n = 2) over 48 h in patients with advanced heart
failure was conducted to assess tolerability, safety, and hemodynamic variables
(Doppler echocardiography).
RESULTS: During tezosentan infusion, no episodes of hypotension requiring
withdrawal of therapy occurred, and hemodynamic rebound was not observed after
abrupt cessation of the infusion. There were no reports of worsening heart
failure in tezosentan-treated patients up to 28 days following the infusion. The
most common side effect during the infusion was headache (9 of 12
tezosentan-treated patients and both dobutamine-treated patients).
Echocardiographic Doppler measurements suggested improvements in cardiac index,
pulmonary capillary wedge pressure, and relaxation properties as well as in
diastolic and systolic function in all treatment groups.
CONCLUSIONS: Prolonged, 48-h IV dual endothelin-receptor antagonism with
tezosentan was well tolerated with no new safety concerns emerging. These data
further support the potential role of tezosentan in the treatment of patients
with acute heart failure.
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