PURSUIT trial

The PURSUIT Trial Investigators. Investigators. Inhibition of platelet glycoprotein llb/llla with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998 339 436-443. 

To date, the majority of gene therapy trials undertaken aim to cure not inherited genetic defects, but cancer. The average annual incidence of cancer reported in the USA alone stands at approximately 1.4 million cases. Survival rates attained by pursuit of conventional therapeutic strategies (surgery, chemo/radiotherapy) stand at about 50 per cent. 

There have already been clinical trials of porcine hepatocyte-based bioartificial livers [5, 6]. However, we believe these systems to represent temporary and short-lived approaches. Compelling evidence from recent experiments show that primary porcine liver cells express and release endogenous retroviral particles that are able to infect human cells. However, long term in vivo investigations of patients previously exposed to porcine tissues over a period of 12 year did not show any porcine endogenous retrovirus (PERV) viremia [7]. Therefore, we consider the further pursuit of porcine bioartificial livers the only solution at present with regard to the cell source. However, as an intermediate term alternative human cell sources are in development [8]. Expansion technologies for human fetal cells may contribute to resolve these limitations in the future. 

The AUSAs are the principal trial attorneys for the U.S. government. Each U.S. attorney exercises wide discretion in the use of his or her resources to further the priorities of the local jurisdiction. Discretion and expertise are big factors in case decisions. There may be significant disparity in the experience, interest, and capability of U.S. attorneys offices with respect to their pursuit of cGMP violations. 

Insofar as the scale-up of pharmaceutical liquids (especially disperse systems) and semisolids is concerned, virtually no guidelines or models for scale-up have generally been available that have stood the test of time. Uhl and Von Essen [54], referring to the variety of rules of thumb, calculation methods, and extrapolation procedures in the literature, state, Unfortunately, the prodigious literature and attributions to the subject [of scale-up] seemed to have served more to confound. Some allusions are specious, most rules are extremely limited in application, examples give too little data and limited analysis. Not surprisingly, then, the trial-and-error method is the one most often employed by formulators. As a result, serendipity and practical experience continue to play large roles in the successful pursuit of the scalable process. 

Table 3 summarizes the primary results of these trials. Overall the use of GPIIb/llla inhibitors was associated with a modest, but significant reduction in the primary endpoint in PRISM, PRISM-PLUS, and PURSUIT Treatment benefit was confined to early time points in PRISM (48 hours) and PRISM-PLUS (seven days), but not sustained at 30 days (17,18). In contrast, treatment with eptifibatide reduced the incidence of composite endpoint by 1.5% absolute risk difference (ARD) in PURSUIT which was observed within four days and maintained for 30 days without attenuation or amplification (19). 

FQ (in phase lib of clinical trials) represents the first organometallic antimalarial currently in the pipe-line of promising drugs. Moreover, the pursuit of studies regarding the mechanism of action of FQ and the possible mechanisms of resistance appears promising not only for chemotherapy of malaria, but also as the basis for new concept in drug design. 

Selected scores have been proposed for stratifying risk after MI. These scores have been derived either from clinical trials (TIMI, PURSUIT, GUSTO, etc.) or from registries and cohort studies (PREDICT, CCP, etc.). The majority of them divide the ACS into two groups with and without ST-segment elevation (STE-MI or STE-ACS vs NSTE-MI or NSTE-ACS). This classification is very useful for a better approach of treatment. The GUSTO score includes QRS duration and ECG (Hathaway et al., 1998a,b) prior MI (Table 8.4), and the PREDICT score uses other ECG parameters (ECG severity score) that include ST, Q wave and branch block criteria (Jacobs etal., 1999 Table 8.5). 

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