Clinical trials failures

Human growth hormone, used as a human pharmaceutical, is approved for only one indication in the United States, treatment of growth failure owing to hGH deficiency, a condition known as pituitary dwarfism. However, clinical trials are under way to test its efficacy in Turner s syndrome, bums, wound healing, cachexia, osteoporosis, constitutional growth delay, aging, malnutrition, and obesity. 

Turner s Syndrome. Turner s syndrome is a genetic disorder of females characterized by short stature, nonfunctioning ovaries, and failure to develop secondary sexual characteristics. Several clinical trials in the United States, Europe, and Japan have demonstrated that hGH can accelerate... 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

A number of rationally designed MMP inhibitors have shown some promise in the treatment of pathologies, which MMPs are suspected to be involved in. However, most of these, such as Marimastat (BB-2516), a broad spectrum MMP inhibitor, or trocade (Ro 32-3555), an MMP-1 selective inhibitor, have performed poorly in clinical trials. The failure of Marimastat was partially responsible for the folding of British Biotech, which developed it. The failure of... 

In clinical trials, ATI antagonists have proven to be as effective as ACE inhibitors in hypertension, congestive heart failure, and renal failure [3]. The favorable side effect profile of ATI antagonists argues for a greater use of these diugs. At present, due to still higher costs, they are indicated in patients who do not tolerate ACE inhibitor treatment. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

The importance of CD28 came out when the phase I clinical trial with the humanized monoclonal superagonist of the CD28, TGN1412, resulted in an unexpected cytokine storm with multiorgan failure in 2006 in the UK [71],... 

Clinical experience shows that these cements are durable. For example, a failure rate as low as 2 % has been reported by Mount (1984) in a clinical trial lasting seven years, and Wilson McLean (1988) have cited a number of clinical trials attesting to the durability of this cement. 

Heart failure is more prevalent and associated with a worse prognosis in African-Americans compared to the general population.1 Unfortunately, deficiencies in disease prevention, detection, and access to treatment are well documented in minority populations. African-Americans and other races are underrepresented in clinical trials, compromising the extrapolation of results from these studies to ethnic subpopulations. The influence of race on efficacy and safety of medications used in HF treatment has received additional attention with... 

Although P-blockers should be avoided in patients with decompensated heart failure from left ventricular systolic dysfunction complicating an MI, clinical trial data suggest that it is safe to initiate P-blockers prior to hospital discharge in these patients once heart failure symptoms have resolved.64 These patients may actually benefit more than those without left ventricular dysfunction.65 In patients who cannot tolerate or have a contraindication to a P-blocker, a calcium channel blocker can be used to prevent anginal symptoms, but should not be used routinely in the absence of such symptoms.2,3,62... 

Upon stabilization, placement of a pulmonary artery (PA) catheter may be indicated based on the need for more extensive cardiovascular monitoring than is available from non-invasive measurements such as vital signs, cardiac rhythm, and urine output.9,10 Key measured parameters that can be obtained from a PA catheter are the pulmonary artery occlusion pressure, which is a measure of preload, and CO. From these values and simultaneous measurement of HR and blood pressure (BP), one can calculate the left ventricular SV and SVR.10 Placement of a PA catheter should be reserved for patients at high risk of death due to the severity of shock or preexisting medical conditions such as heart failure.11 Use of PA catheters in broad populations of critically ill patients is somewhat controversial because clinical trials have not shown consistent benefits with their use.12-14 However, critically ill patients with a high severity of illness may have improved outcomes from PA catheter placement. It is not clear why this was... 

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