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Endothelin’s Trials

Several early trials of endothelin blockers showed no benefit for the treatment of many common conditions, but researchers are holding out hope for these current and soon-to-begin human studies.

By Rachael Moeller Gorman // Winter 2010
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Past Trials:

 

TRIAL NAME

CONDITION

DRUG

STATUS

RESULTS

POSSIBLE REASONS FOR FAILURE

REACH-1 (Research on ET Antagonism in Chronic Heart Failure) Heart failure 500 mg bosentan Published June 1999 Stopped early due to liver problems, but some patients showed signs of reduced risk of heart-failure-related death Perhaps not continued long enough to establish a significant survival benefit
BMS-193884
Erectile dysfunction 100 mg BMS-193884 Published January 2002 Did not improve erectile function Simply ineffective
ENABLE (ET Antagonist Bosentan for Lowering Cardiac Events in Heart Failure)
Heart failure 125 mg bosentan Results presented March 2002 Bosentan did not improve survival; in fact, it seemed to confer an early risk of worsening heart failure Perhaps the result of fluid retention caused by the ET blocker or the bosentan dose was suboptimal
RITZ-4 (Randomized Intravenous Tezosentan)
Heart failure 50 mg per hour tezosentan Published May 2003 Didn’t improve outcome (worsening heart failure, recurrent ischemia, death) Dose may have been suboptimal


Current Trials:

 

TRIAL NAME

CONDITION

DRUG

STATUS

WHAT IT’S TESTING

WHY IT MIGHT WORK

NCT00777985; University Hospital, Grenoble, France Cardiovascular consequences of obstructive sleep apnea 62.5 mg bosentan for four weeks Currently recruiting; estimated completion, February 2010 Comparing bosentan with a CPAP machine, which creates positive air pressure in the sleeper’s airways, keeping breathing free and lowering blood pressure Blocking ET receptors may have the same blood-pressure-lowering effects as using a CPAP machine
NCT00815347; University of Connecticut Health Center
Poorly controlled asthma 125 mg bosentan for four weeks, and then 250 mg bosentan for four weeks Currently recruiting; estimated completion, June 2010 Whether bosentan can help patients who remain symptomatic despite controller therapy ET plays a role in smooth muscle constriction as well as in inflammation and uncontrolled immune responses, as occur in asthma
NCT00617669; AstraZeneca
Metastatic hormone-resistant prostate cancer 10 mg zibotentan + docetaxel Currently recruiting; estimated completion, March 2012 Whether zibotentan can improve the ability of chemotherapy drug docetaxel to slow prostate cancer Animal experiments have shown that adding ET receptor antagonists to standard chemotherapy decreases prostate tumor growth more than either agent alone does
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Endothelin: Still Beyond Reach

endothelin

The protein endothelin shows up everywhere, so scientists hoped blocking its action could treat many diseases. It hasn’t happened—yet.

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