Open-label comparative trials

Box 5.7 An Open-label Comparative Trial with Blinded Assessments... 

Recent data from a kidney pancreas induction study suggests that 2 doses of Daclizumab (2 mg/kg) at day 0 and day 14 is equivalent to 5 doses of 1 mg/kg every 14 days. (Stratta AJ, Alloway RR, Hodge E et al. A multicenter, open-label, comparative trial of two Daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients interim analysis. Clin Transplant 2002 l6(l) 60-8.)... 

The Superior Yield of the New Strategy of Enoxaparin Revascularization and GP llb/llla Inhibitors (SYNERGY) trial (20) was a randomized, open-label, international trial comparing enoxaparin and UFH among 10,027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy. The incidence of the composite primary efficacy endpoint (death/MI at 30 days) was similar in enoxaparin and UFH-treated patients (14.0% vs. 14.5%,... 

Murray MD, Deer MM, Ferguson JA, et al. Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med 2001 111 513-520,... 

Khan OA, Tslis AC, Kamholz JA, Garbem JY, Lewis RA, Lisak RP (2001b) A prospective open-label treatment trial to compare the effect of IFN beta-la (Avonex), IFN beta-lb (Betaseron) and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remit-ting multiple sclerosis Results after 18 months of therapy. Mult Scler 7 349-353. 

Diamant M, Van Gaal L, Stranks S, Northmp J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3) an open-label randomised trial. Lancet 2010 375 2234-A3. 

A prospective open-label, randomised trial comparing 14days of primaquine (0.25 mg base/kg) with either artensunate-amodiaquine or dihydroartemisinin-piperaquine (DHP) for the treatment of uncomplicated monoinfection with Plasmodium vivax malaria was performed Patients were randomised and given treatments without testing for G6PD status. Of the 331 patients, intravascular haemolysis occurred in 5 patients, of which 3 were males hemizygous for the G6PD-Mahidol mutation. Minor side effects were more frequent with artensunate-amodiaquine. 

Kozlowski A, Charles SA, Harris JM (2001) Development of pegylated interferons for the treatment of chronic hepatitis C. BioDrugs 15 419 29 Krown SE, AeppU D, Balfour HH Jr (1999) Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol 20 245-254 LaFleur DW, NardeUi B, Tsareva T, Mather D, Feng P, Semenuk M, Taylor K, Buergin M, Chinchilla D, Roshke V, Chen G, Ruben SM, Pitha PM, Coleman TA, Moore PA (2001) Interferon-kappa, a novel type I interferon expressed in human keratinocytes. J Biol Chem 276 39765-39771... 

A large open-label flexible dose study (Sanchez-Lacay etal, 2001) utilizing nefa-zodone in the treatment of major depression in a predominantly monolingual, Hispanic Caribbean population (Dominican Republic, Puerto Rico, and Cuba) revealed similar response rates and an endpoint mean dosage when compared to previous nefazodone trials with non-Hispanic patients. No serious adverse events were reported, but 42% of the subjects did not complete the study for various reasons including side effects, family, or work responsibilities. 

Treatment of symptomatic diverticular disease of the colon is aimed at the relief of symptoms and the prevention of major complications. The efficacy of fiber supplementation and of anticholinergic and spasmolytic agents remains controversial. Antibiotics are commonly used in the treatment of inflammatory complications of diverticular disease. Data from open labelled and randomized controlled trials do suggest the efficacy of rifaximin in obtaining symptomatic relief in patients with diverticular disease. Approximately 30% therapeutic gain compared to fiber supplementation only can be expected after one year of intermittent treatment with rifaximin. Considering the safety and tolerability of rifaximin, this drug can be recommended for patients with symptomatic uncomplicated diverticular disease. 

Fluphenazine, a typical neuroleptic of the phenothi-azine class, has been less widely used for treatment of tics than haloperidol or pimozide. A controlled trial of haloperidol, fluphenazine, and trifluoperazine found comparable tic-reducing efficacy, but greater sedation and extrapyramidal side effects for haloperidol fluphenazine was the best tolerated (Borison et al., 1982). In an open-label trial with 21 subjects who had an unsatisfactory response to haloperidol, fluphenazine had a superior side effect profile to that of haloperidol in the dose range employed (mean dose of fluphenazine, 7 mg/day, range 2-15 mg/day) (Goetz et al., 1984). In this group selected for an unsatisfactory response to haloperidol, 11 of the 21 subjects (52%) had a better response to fluphenazine than haloperidol, 6 subjects had a comparable response, and 2 subjects preferred haloperidol. 

In the Zito et al. study (2000), antidepressants were the second most commonly prescribed psychotropic medication. There are a total of 10 studies or case reports in the literature examining antidepressant use in preschool children (Table 49.4). None of the 10 studies are randomized, double-blind, or placebo-controlled trials. The ten uncontrolled studies looked at a total of 37 preschool children. Six of the studies looked at a total of 29 preschoolers with autism or childhood schizophrenia (Campbell et ah, 1971a Petti and Campbell, 1975 Holttum et ah, 1994 Sanchez et ah, 1996 DeLong et ah, 1998 Hollander et ah, 2000). While these six studies are difficult to compare, given the small sample sizes and the different treatment medications, these open-label studies suggest that clomipramine, venlafaxine, and fluoxetine may be helpful to reduce some psychiatric symptoms found in autistic... 

The second Serono trial was a multicenter randomized study of Rebif at 44 mg subcutaneously three times per week compared to Avonex at 30 mg intramuscularly weekly. The primary efficacy outcome was the incidence of exacerbations through week 24. Avonex was administered according the recommended regimen in the FDA-approved labeling, and / eb/f according to the recommended regimen in Serono s proposed labeling. Serono elected to conduct the study open label, but with a blinded clinical evaluator. 

Namjoshi and coworkers (297) reported the results of an extension phase study comparing olanzapine with placebo. The initial reduction achieved in YMS scores continued during this period and by the end of the extension phase reached a mean reduction of 18-points. The authors also conducted an economic analysis of the drug trial (excluding the acute treatment period) and found that the cost per month seen in the open-label extension phase (i.e., 649) was about half of that observed during the 12 months before entering the study (i.e., 1,533.)... 

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