Double-blind placebo-controlled trial

Dorus and colleagues (1989) conducted a multicenter, double-blind, placebo-controlled trial in depressed and nondepressed alcoholic veterans. A total of 457 male alcoholic patients, of whom approximately one-third were depressed, were randomly assigned to receive either 600-1,200 mg/day of lithium or a comparable number of placebo capsules. No significant differ-... 

Fawcett J, Clark DC, Aagesen CA, et al A double-blind, placebo-controlled trial of lithium carbonate therapy for alcoholism. Arch Gen Psychiatry 44 248-2 56,1987... 

Covey LS, Classman AH A meta-analysis of double-blind placebo controlled trials of clonidine for smoking cessation. Br J Addict 86 991—998, 1991 Covey LS, Classman AH, Stetner F Naltrexone effects on short-term and long-term smoking cessation.] Addict Dis 18 31 0, 1999 Covey LS, Sullivan MA, Johnston A, et al Advances in non-nicotine pharmacotherapy for smoking cessation. Drugs 39 17-31, 2000 Dani JA, De Biasi M Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav 70 439 46, 2001... 

Rogers SL, Friedhoff LT (1996). The efficacy and safety of Donepezil in patients with Alzheimer s disease results of a US multicentre, randomised, double-blind, placebo-controlled trial. Dementia ,... 

The current use of IV rt-PA for acute stroke thrombolysis is based on the NINDS rt-PA study, a two-part randomized, double blind, placebo-controlled trial. " This trial was preceded by two open-label, dose-escalation safety studies that suggested that treatment within 180 minutes of stroke onset, and rt-PA dosages no higher than 0.95 mg/kg, was safe and effective. ... 

E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas R Randomised double-blind placebo-controlled trial of thrombol3ffic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 352 1245-1251. 

Microplasmin is a truncated form of plasmin that is more resistant to the effects of antiplasmin. In a rabbit stroke model, intravenous microplasmin infusion resulted in a high rate of clot lysis without increasing the rate of ICH. In addition, there was significant improvement in the behavioral rating scores, suggesting a neu-roprotective effect. The ongoing MITI-IV trial is a 40-patient multicenter, double-blind, placebo-controlled trial using three different intravenous doses of microplas-min to treat acute ischemic stroke (NIHSS >6 and <22) within 12 hours of symptom onset. 

Lodder J, van Raak L, Hilton A, Hardy E, Kessels A. Diazepam to improve acute stroke outcome results of the early gaba-ergic activation study in stroke trial. A randomized double-blind placebo-controlled trial. Cerebrovasc Dis 2006 21 120-127. 

The Trial of Org 10172 in Acute Stroke Treatment (TOAST) was a randomized, double-blind, placebo-controlled trial of danaparoid in 1281 patients within 24 hours of onset of acute ischemic stroke. A three-stage dosage regime was used to achieve plasma anti-factor Xa activity of 0.8 unit/mL. Favorable outcome was defined as the combination of a Glasgow Outcome Scale (GOS) score of 1 or 2 and a modified Barthel Index (BI) score of 12 or greater (on a scale of 0-20) at 3 months or 7 days. Very favorable outcome required the combination of a GOS score of 1 and a Barthel Index (BI) score of 19 or 20 at 3 months or 7 days. 

Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH) randomised, double-blind, placebo-controlled trial. Lancet 2004 364(9431) 331-337. 

Rogers, SL, Farlow, MR, Doody, RS, Mohs, R, Friedhoff, LT and the Donepezil Study Group (1998) A 24-week, double blind, placebo-controlled trial of donepezil in patients with Alzheimer s disease. Neurology 50 136-145. 

Only one study to date has been conducted on the treatment of acute pancreatitis with antioxidants. Clemens et al. (1991) were unable to show any difference in the incidence or severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a prospective, randomized, double-blind, placebo-controlled trial of allopurinol. However, Salim (1991) performed a similar trial of the effect of allopurinol and DMSO in patients with pain from recurrent pancreatitis, and found significant benefit. On the basis that depletion of antioxidants is important in the pathogenesis of chronic pancreatitis, the administration of a cocktail of antioxidants was assessed for its effect on pain in this disease. Treatment with a combination of organic selenium, d-carotene, vitamins C and E, and methionine was of benefit in the initial pilot study, and in a placebo-controlled trial (San-dilands etal., 1990 Uden et al., 1990). 

Megraud F, Lamouliatte H. The treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther 2003 17 1333-1343. Silverstein FE, Graham DY, Senior IR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving non-steroidal anti-inflammatory drugs a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995 123 241-249. 

A randomized, double-blind, placebo-controlled trial evaluating the use of a monophasic OC containing 30 meg ethinyl estradiol and 3 mg drospirenone, a progesterone with anti-androgenic effects, showed improvement in the treatment arm compared with placebo.31 In particular, appetite, food cravings, and acne improved. However, active treatment was not associated with a statistically significant improvement in the overall outcome measure, the Calendar of Premenstrual Experiences (COPE) scale, perhaps because of the small sample size (n = 82). 

Lecrubier, Y., Clerc, G., Didi, R. Kieser, M. (2002). Efficacy of St. John s Wort extract WS 5570 in major depression a double-blind, placebo-controlled trial. Am. J. Psychiatry, 159, 1361-6. 

Di Bisceglie, A. M., et al. (1989). Recombinant interferon alpha therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N. Engl. J. Med. 321,1506-1510. 

Graydon, R, SE Gilchrist, IS Young, U Obermuller-Jevic, O Hasselwander, and JV Woodside. 2007. Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3 a double-blind, placebo-controlled trial. EurJ Clin Nutr 61(10) 1196-2000. 

Gionchetti P, Rizzello F, Ferrieri A, Venturi A, Brignola C, Ferretti M, Peruzzo S, Miglioli M, Campieri M Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroid-treatment A double-blind, placebo-controlled trial. Dig Dis Sci 1999 44 1220-1221. 

Taylor DN, MacKenzie R, Durbin A, Carpenter C, Atzinger CB, Haake R, Bourgeois AL Double-blind, placebo-controlled trial to evaluate the use of rifaximin (200 mg TID) to prevent diarrhea in volunteers challenged with Shigella Jlexneri 2a (2457T). Am J Trop Med Hyg 2004 71(suppl 4) 1-303 (abstract No. 2079). 

In 1990, Burke et al. [29] published a double-blind, placebo-controlled trial on the use of oral tobramycin in acute UC. Eighty-four patients were randomized to receive steroid plus tobramycin or placebo. After 1 week of treatment, 74% of patients in the tobramycin treatment group versus 43% in the placebo group (p < 0.003) achieved a complete remission. Subsequently, tobramycin and metronidazole were associated with a standard steroid treatment in severely acute UC. At the end, no difference was found between the two groups [30]. 

Sharara AI, Aoun E, Mounzer R, Sidani S, El Hajj I Rifaximin in abdominal bloating and flatulence trial (RAFT) A randomized double-blinded, placebo-controlled trial. Am J Gastroenterol 2004 99(suppl) S281. 

Although there is some evidence for the efficacy of long-term treatment with rifaximin for symptomatic relief in patients with uncomplicated diverticular disease, an unresolved issue is whether rifaximin can prevent major inflammatory complications of diverticular disease. In the two prospective open trials discussed above, the occurrence rate of complications in 12 months was lower in patients treated with glucomannan plus rifaximin compared to patients treated with glucomannan only 2.7 versus 0.9% [43] and 3.2 versus 1.3% [44], This observation was not confirmed in the double-blind placebo-controlled trial [45] in which no difference in the 1-year complication rate was observed between the rifaximin and placebo groups. However, in all the studies, the number of patients suffering complications in a 12-month period was too small to detect any statistically significant... 

No definitive conclusions can be drawn concerning a possible role of rifaximin in preventing major complications of diverticular disease. Double-blind placebo-controlled trials with an adequate sample size are needed. However, such trials are difficult to perform considering the requirement of a large number of patients. Assuming a baseline risk of complications of diverticular disease of 5% per year [2], a randomized controlled trial able to detect a 50% risk reduction in complications should include 1,600 patients per treatment group considering a power of 80% (1 - (3) and an a error of 5%. 

Since a high spontaneous cure rate has often been observed [40], double-blind, placebo-controlled trials are needed to definitely assess the efficacy of rifaximin in the treatment of BV. 

Ahmed-Jushuf IH, Shahmanesh M, Arya OP The treatment of bacterial vaginosis with a 3-day course of 2% clindamycin cream Results of a multicenter, double-blind, placebo-controlled trial. Genitourin Med 1995 71 254— 266. 

The observation that women with breast cancer receiving tamoxifen had a reduced incidence of contralateral cancer was the basis for the NSABP-PI study, a randomized, double-blind, placebo-controlled trial that began in 1992. The main objective was to ascertain whether tamoxifen might effectively reduce the risk for breast cancer in women with a high risk of developing this disease. A total of 13,388 women > 35 years old were randomized to either tamoxifen (20 mg/d) or placebo for 5 years. In 1998, the trial was prematurely interrupted as the hypothesis of the study was confirmed (Fisher et al. 1998). However, the reduction in breast cancer risk with tamoxifen was accompanied by an increase in the incidence of invasive endometrial cancer (mean RR = 2.53). The increased risk was seen principally among women > 50 years old with a RR of 4.01, while among women < 49 years old the RR was 1.21. 

Ichinose, Y. et al., Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma, J Natl Cancer Inst, 95, 605, 2003. 

Ben-Menachem, E., Soderfelt, B., Hamberger, A., Hedner, T., and Persson, L. I. (1995) Seizure frequency and CSF parameters in a double-blind placebo controlled trial of gabapentin in patients with intractable complex partial seizures. Epilepsy Res. 21,231-236. 

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