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 |
