Clinical trials multicenter evaluations

Hernandez, M., Nieto, J.A., Sobradillo, B., Pombo, M., Ferrandez, D., and Rejas, J. (1991). Multicenter clinical trial to evaluate the therapeutic use of recombinant human growth hormone from mammalian cells in the treatment of growth hormone neurosecretory dysfunction. Hormone Res. 35,13 18. 

Asthma-related death and life-threatening exacerbations occurred in the Salmeterol Multicenter Asthma Research Trial and may have been associated with regular use of salmeterol [27]. These event are rare, but were observed primarily in African Americans. The US Food and Drug Administration has added a black box warning to LABA labels reflecting the observations from this trial. A meta-analysis of 19 clinical trials to evaluate the safety of LABAs concluded that they were associated with increased hospitalization for asthma exacerbation, severe asthma exacerbation, and asthma-related death [28],... 

In 1975, the first commercial entity was formed to provide multicenter, outpatient clinical trial contracting services in the United States. This was the beginning of the modern Contract Research Organization (CRO) industry. It is now composed of thousands of domesfic and infernafional firms involved in medical producf evaluations in humans. The total annual expense globally for clinical trials and related functions necessary for commercial, governmenf, and academic therapeutic product development is estimated at US 50 billion, of which about US 15 billion is outsourced to the contract services market. 

Hawthorn has long been used as a medicinal substance, and an extract such as WS 1442, a formulation of hawthorn leaves with flowers, has been evaluated in different studies for treatment of heart failure (40 2). Patients with New York Heart Association class II heart failure participated in a placebo-controlled, randomized, multicenter trial. They received 30 drops of the extract three times daily for eight weeks. At the end of the study, heart failure condition was improved (41). A meta-analysis of available clinical trials suggests that the extract is useful as an adjunct treatment for patients with mild to moderate heart failure (42). Therefore, it is likely that hawthorn products would be administered together with digoxin in clinical management of patients (Fig. 4). 

The Estradiol to Cure Restenosis (ESTRACURE) trial is a randomized clinical trial of 360 patients undergoing stent implantation evaluating the efficacy and safety of local l7(3-estradiol delivery prior to stent implantation to reduce angiographic late luminal loss and restenosis, The hypothesis of this prospective, randomized, multicenter trial is that a single local administration of 17(3-estradiol will improve vascular healing and reduce late... 

Elliott, G.T., McLeod, R.A., Perez, J., von Eschen, K.B. Interim results of a phase II multicenter clinical trial evaluating the activity of a therapeutic allogeneic melanoma vaccine (theraccine) in the treatment of disseminated malignant melanoma. Semin Surg Oncol 9 (1993) 264-272. 

Based on experimental and clinical data, cerebral hypothermia appears to be a potent therapeutic approach to treating brain trauma. However, recent results from the Multicenter National Brain Injury Study Hypothermia (NABIS H) clinical trial appear to be disappointing, and more refinement of the clinical application of hypothermia is required (73). Additional clinical trials are now required to evaluate systematically the beneficial effects of clinical hypothermia in different populations of brain-injured patients. In addition, experimental data regarding the beneficial effects of combination therapy are required to evaluate whether hypothermia plus pharmacotherapy may provide a better outcome. Forexample, mildpostischemichypothermia(33-39°C) combined with the antiinflammatory cytokine IL-10 has recently been reported to produce long-term protection of the C Al hippocampus after transient global ischemia (74). Hypothermia or IL-10 treatment alone did not protect chronically. In contrast, Kline etal. (75) showed that acute systemic administration of IL-10 suppressed the beneficial effects of... 

Contract research organizations can provide services for clinical trials whether they are the simplest phase 1 safety and tolerance studies or complex multicenter phase 3 efficacy and safety studies. Table 3 identifies specific activities that may be considered for outsourcing. These activities are grouped according to four major categories management of the study conduct at clinical sites, data management, data evaluation, and summarization. 

To date, one clinical dial has evaluated the role of nimocUpine in the heatment of HAD. A multicenter phase I/II study by the AIDS CUnical Trial Group enrolled 4l patients with cUfferent degrees of HAD (Navia et al., 1998). Patients were assigned to one of three arms placebo, nimocUpine 30mg orally del or nimocUpine 50 mg five times a clay for 16 weeks. Patients in all arms received an NRTI (ziclovucUne, cUclanosine... 

These findings prompted the development and evaluation of the currently available form of inhaled tobramycin, which is sterile and free of preservatives. The benefit of maintenance therapy with this inhaled tobramycin is supported by the results from two 24-week, multicenter, randomized, double blind, placebo-controlled clinical trials [6]. In these studies, patients with cystic fibrosis were at least six years of age, with an FEVj between 25% and 75% predicted. All subjects had evidence of colonization with Pseudomonas aeruginosa. Exclusion criteria included an elevated serum creatinine or colonization with Burkholderia cepacia, which is typically resistant to tobramycin. Subjects in the active treatment arm received inhaled tobramycin 300 mg twice daily through... 

Two percutaneous aortic valves have recently received CE Mark approval (CoreValve in May 2007 and Edwards-Sapien in September 2007) and several other valved stent designs are in development with first-in-man reports or in preclinical testing. Only the Edwards-Sapien valve is currently undergoing evaluation in a randomized multicenter clinical trial against surgery in the Elnited States. 

Phase II clinical trials are designed to evaluate the producfs efficacy and side-effect profile. About 100-300 patients are involved. Data obtained are used to characterize the dose-response relationship. The costs involved are about 10-100 million Euro over 1- to 2-year period. The success rate is about 40%. Studies performed may be characterized by a single or multicenter study, single- or double-blinded with a control group and randomization of the patients. Amongst the most common reasons for failure at this phase are poorly designed studies and ineffective or unsafe products. 

Czako, Ini J. Clin. Pharmacol Ther. Toxicol. 18, 229(1980), Clinical-pharmacological evaluation E. Torok el al, ibid. 200. GC-MS deiermn in plasma E. Tomori, E. Elekes, J. Chromatog. 204, 355 (1981). Multicenter clinical trial E. Tordk ef al, InL J. Clin. Pharmacol. Ther. Toxicol. 23, 650 (1985). 

Hidler, J., Nichols, D., Pelliccio, M., Brady, K., Campbell, D.D., Kahn, J.H., Homby, T.G. Multicenter randomized clinical trial evaluating the effectiveness of the Lokomat in subacute stroke. Neurorehabilitation and Neural Repair 23(1), 5-13 (2009)... 

Reproduced with permission from Wolters Kluwer Health, Inc. Rosen, C.L., Steinberg, G.K., Demonte, R, Delashaw Jr., J.B., Lewis, S.B., Shaffrey, M.E., Aziz, K., Hantel, J., Marciano, RR, 2011. Results of the prospective, randomized, multicenter clinical trial evaluating a biosynthesized cellulose graft for repair of dural defects. Neurosurgery 69, 1093-1103... 

CAD techniques for CTC have advanced substantially during the last several years. As a result, a fundamental CAD scheme for the detection of polyps has been established, and commercial products are now available. Thus far, CAD shows the potential for detecting polyps and cancers with high sensitivity and with a clinically acceptable low false-positive rate. However, CAD for CTC needs to be improved further for more accurate and reliable detection of polyps and cancers. There are a number of technical challenges that CAD must overcome, and the resulting CAD systems should be evaluated based on large-scale, multicenter, prospective clinical trials. If the assistance in interpretation offered by CAD is shown to improve the diagnostic performance sub-... 

The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a follow-up randomized, double-blind, parallel-conlrolled clinical trial of CRT in New York Heart Association Functional Class II heart failure patients on optimal medical therapy with a left ventricular ejection fraction < 0.35, a QRS > 130ms and a Class I indication for an ICD. Patients were randomized to control group (ICD activated, CRT off) and to CRT group (ICD activated, cardiac-resynchronization therapy on). No significant differences were noted in 6-min walk distance or quality of life scores or peak V02. There were significant improvements in left ventricular diastolic and systolic volumes and in left ventricular ejection fraction (198). 

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