November 08, 2007
VERITAS
Which means, of course, "truth," hubris at its best to so name a trial. And there are several.
One studying AMD (macular degeneration) "helps retinal physicians determine the best therapy for their patients" but hardly the truth.
The latest, the Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies, purports to determine if this new drug improves outcomes in patients with acute heart failure. (While we are on study names, this one relies on RITZ, ESCAPE and REVIVE. The footnotes also mention LIFE, DANAMI 2, MADIT-2, MIRACLE-ICD, OVERTURE, OCTAVE, ENABLE 1 & 2, CHRISTMAS, AFFIRM, RACE, WIZARD, AZACS, REMATCH, BNP trial and HARDBALL; CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE.)
Their conclusions: "Tezosentan also had no effect on the primary mortality/morbidity composite outcome (or any of the secondary outcomes), though even with this end point we had 80% power to detect a 25% relative risk reduction. Although disappointing and contrary to expectations based on the potential pathophysiological role of endothelin-1 in heart failure, our findings are consistent with earlier trials in chronic heart failure.27-30 In those trials, long-term treatment with oral endothelin receptor antagonists had no effect on left ventricular remodeling or clinical outcomes.27-30 Conceptually, however, short-term intravenous administration of a drug might have less prospect of showing a longer-term effect on morbidity and mortality outcomes, emphasizing the difficulty in evaluating new treatment for acute heart failure. Despite its hemodynamic actions, milrinone did not reduce morbidity and mortality in Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF), and nesiritide does not reduce morbidity or mortality in acute heart failure.31-33 Of course, it is also possible that a beneficial effect of tezosentan in one subgroup of patients may have been offset by harm in another, eg, patients with a low baseline blood pressure. VERITAS did not, however, have the statistical power for such an analysis, which in any case could only be hypothesis-generating.
"In summary, tezosentan, a treatment with "favorable" hemodynamic actions, failed to improve breathlessness or reduce fatal and nonfatal cardiovascular events in patients following an emergency admission to hospital with acute heart failure. So far, it has proved impossible to identify a therapeutic role for endothelin antagonists in patients with acute or chronic heart failure."
So from a mechanistic standpoint, this drug should work. Yet the previous studies on this type of drug showed no benefit. That was confirmed by this study.
This study was done at centers scattered around the world. It was paid for by the Swiss firmed that partnered with Genetech in 2000 to bring this drug into the US. They have known for years that it is not the wonder drug they thought. But I have no doubt it will continued to be pushed and tested until some sub-group of CHF patients is found who show some measurable but meaningless improvement.
At least the VERITAS revealed a small slice of the truth.
| By Robert Maddox | 11:22 PM