CUnical trial

May S, Letendre S, Haubrich R, McCutchan JA, Heaton R, CappareUi E, EUis R (2007) Meeting practical chaUenges of a trial involving a multitude of treatment regimens an example of a multi-center randomized controUed cUnical trial in neuroAIDS. J Neuroimmune Pharmacol 2(1) 97-104... 

The CTC system was the scheme used for the control of clinical trials before the introduction of CTX in 1981. Most clinical trials are now conducted under the CTX scheme. The CTX scheme was devised to speed up review and approval of cUnical trials to allow important drugs to enter trials with minimum delay. Identical data are submitted for the filing of CTC and CTX the difference is that, for CTX, only a summary of raw data is required. Information for submission is in three parts ... 

Cleland JG, Ghosh 1, Freemantle N, Kaye GC, Nasir M, Clark AL, Coletta AP (2004) CUnical trials update and cumulative meta-analyses from the American College of Cardiology WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure, Eur 1 Heart Fail 6 501-508 Cohen LM, CoUins FL, Britt DM (1997) The effect of chewing gum on tobacco withdrawal. Addict Behav 22 769-773... 

What information will expedite and optimise design of cUnical trials if the compound progresses to full development (ED) ... 

Experience so far from cUnical trials has shown these agents can be well tolerated at biologically active doses. However, cardiac toxicity, mainly QTC prolongation, and cardiac arrhythmias, including atrial fibrillation and tor-... 

Alakhov V, Klinski E, Li SM, Pietrzynski G, Venue A, Batrakova E, Bionitch T, Kabanov A. Block copolymer-based formulation of doxombicin. From cell screen to cUnical trials. Colloid Surf B Biointerfaces 1999 16 113-134. 

The treatment of thalassemia, as in other metal overload disorder, is chelation therapy. The chelating agent most widely nsed is deferoxamine administered subcutaneously. The search for an orally administered iron chelator has intensified in recent years, leading to cUnical trials of many potential new iron chelators snch as deferiprone(Ll). However, many issues regarding the nse of these drugs, such as dose-related toxicity and recommended age of initiation, remain unresolved. " ... 

Easty DL, Rice NSA, Jones BR. CUnical trials of topical sodium cromoglycate in aUergic conjunctivitis. CUn AUergy 1972 2 99-107. 

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... 

While the use of a placebo treatment can pose ethical problems, it is often preferable to the continued use of treatments of unproven efficacy or safety. The ethical dilemma of subjects suffering as a result of receiving a placebo (or ineffective drug) can be overcome by designing cUnical trials that provide mechanisms to allow them to be withdrawn ( escape ) when defined criteria are reached, e.g. blood pressure above levels that represent treatment failure. 

Whitehead J 1992 The Design Analysis of Sequential CUnical Trials, 2nd Edition. Ellis Horwood, Chester. 

Wilson SE, Nord CE. CUnical trials of extended spectrum penicillin/beta-lactamase inhibitors in the treatment of intra-abdominal infections. European and North American experience. Am J Smg 1995 169(Suppl 5A) S21-6. 

Wohnark N, Rockette H, Mamonnas E, Jones J, Wieand S, Wickerham DL, Bear HD, Atkins JN, Dimitrov NV, Glass AG, Fisher ER, Fisher B. CUnical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes B and C carcinoma of the colon results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol 1999 17(ll) 3553-9. 

Bing C, Yun-sheng L. Randomised double-bUnd cUnical trial of moderate dosage naloxone in acute moderate and severe traumatic brain injury. BuU Hunan Med Univ 2002 27 58-60. 

Krogstad P, Lee S, Johnson G, Stanley K, McNamara J, Moye J, Jackson JB, Aguayo R, Dieudoime A, Khoury M, Mendez H, Nachman S, Wiznia A, BaUow A, Aweeka F, Rosenblatt HM, Perdue L, Frasia A, Jeremy R, Anderson M, Japour A, Fields C, Farnsworth A, Lewis R, Schnittman S, GigUotti M, Maldonaldo S, Lane B, Hernandez JE, et al Pediatric AIDS CUnical Trials Group 377 Study Team. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nehinavir, or ritonavir for pretreated children mfected with human immnnodeficiency virus type 1. Qin imect Dis 2002 34(7) 991-1001. 

Banham SW, Moran F. A cUnical trial of oxatomide in asthma. Br J Clin Pract 1980 34(ll-12) 323-6. 

Beydoun A, Sachdeo RC, Rosenfeld WE, Krauss GL, Sessler N, Mesenbrink P, Kramer L, D Souza J. Oxcarbazepine monotherapy for partial-onset seizures a multicenter, double-bUnd, cUnical trial. Neurology 2000 54(12) 2245-51. 

Newman, D. J., Cragg, G. M. Advanced preclinical and cUnical trials of natmal products and related compounds from marine somces. Curr. Med. Chem. 2004,11, 1693-1713. 

Lee SJ, Zelen M (2000). CUnical trials and sample size considerations another perspective. Statist Sci 15 95-110. 

Overall cUnical trial objectives Specification of the overall objectives of the clinical trial... 

P. F. Thall and K. E. Russell, A strategy for dose-finding and safety monitoring based on efficacy and adverse outcomes in phase FII cUnical trials. Biometrics 54 251-264... 

E. N. Jonsson and L. B. Sheiner, More efficient cUnical trials through use of scientific model-based statistical tests. Clin Pharmacol Ther 72 603-614 (2002). 

Abrams DI, Hilton JF, Leiser RJ, et al (2003) Short-term effects of cannabinoids in patients with HIV-1 infection. A randomized, placebo-controUed cUnical trial. Ann Intern Med 139 258-266... 

Buist DSM, LaCroix AZ, Black DM, et al. Inclusion of older women in randomized cUnical trials Factors associated with taking smdy medication in the Fracture Intervention Trial. J Am Geriatr Soc 2000 48 1126— 1131. 

Appel LJ, Moore TJ, Obarzanek E, et al. A cUnical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med 1997 336 1117-1124. 

Dom J, Naughton J, Imamura D, Trevisan M. Results of a multicenter randomized cUnical trial of exercise and long-term survival in myocardial infarction patients The National Exercise and Heart Disease Project (NEHDP). Circulation 1999 100 1764-1769. 

Fondaparinux has been shown in two recent cUnical trials to be a safe and effective alternative to enoxaparin and intravenous UFEf for the treatment of VTE (see Table 19-17). In the MATISSE DVT trial, a fixed-dose regimen of fondaparinux (7.5 mg/day) given by subcutaneous injection was compared with the standard weight-adjusted dosing of enoxaparin (1 mg/kg every 12 hours) for the acute treatment of DVT followed by 3 months of warfarin therapy. In the MATISSE PE trial, fondaparinux (7.5 mg subcutaneously every 24 hours) was compared with UFH administered by intravenous infusion. In both trials, the dose of fondaparinux was increased to 10 mg subcutaneously every 24 hours for patients who weighed more than 100 kg and reduced to 5 mg every 24 hours for those who weighed less than 50 kg. Fondaparinux received FDA approval for the acute treatment of DVT and PE in 2004. 

Major P, LortUolary A, Hon J, et al. Zoledronic acid is superior to pamidronate in tUe treatment of Uypercalcemia of maUgnancy a pooled analysis of two randomized, controlled cUnical trials. J CUn Oncol 2001 19 558-567. 

Young N, Speck B. Antithymocyte and antilymphocyte globulins CUnical trials and mecUanism of action. In Young S, et al, eds. Aplastic Anemia. Stem Cell Biology and Advances in Treatment. New York, AlanRLiss, 1984 221-226. 

---