Salmeterol compared with slow-release terbutaline in nocturnal asthma A multicenter, randomized, double-blind, double-dummy, sequential clinical trial

Brambilla C, Chastang C, Georges D, Bertin L. Salmeterol compared with slow-release terbutaline in nocturnal asthma. A multicenter, randomized, double-blind, double-dummy, sequential clinical trial.
The aim of the multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial with a 2-week treatment period was to compare the efficacy and safety of salmeterol (50 ug twice daily) with slow-release (SR) terbutaline (5 μg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50-90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7-d run-in period was included in the study. Patients were centrally randomized with a national computer network (Minitel®). The main variable (number of awakening-free nights during the last week of treatment) was analyzed according to a sequential method with the one-sided triangular test. The number of awakening-free nights (± SD) was significantly higher in the salmeterol group: 5.3 ± 2.4 vs 4.6 ± 2.3 (P = 0.006). Salmeterol was significantly more effective than SR-terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 ± 1091/min^-1 vs 332 + 105 I/min^-1, P = 0.04), PEF diurnal variation 6 ± 10% vs 11 ± 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes ( P =0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04). This study confirms that salmeterol, 50 μg twice daily, is particularly useful in controlling nocturnal symptoms of asthma: as compared with the control group, twice as many salmeterol-treated patients were totally free of nocturnal symptoms after 2 weeks of treatment.     

Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial.

BACKGROUND: Famciclovir, the well absorbed oral pro-drug of penciclovir, is effective in the treatment of herpes zoster when given three times daily. Because the intracellular half-life of penciclovir triphosphate in varicella-zoster virus (VZV)-infected cells (7h) is considerably longer than that of aciclovir triphosphate (1h), it may be possible to administer famciclovir less frequently than three times daily for herpes zoster: aciclovir is administered five times daily. METHODS: 559 immunocompetent adults presenting with herpes zoster whose skin lesions were present for less than 72 h were randomized to receive famciclovir 750 mg once daily (od), 500 mg twice daily (bid), or 250 mg three times daily (tid), or aciclovir 800 mg five times daily. All treatments were given for 7 days. Participants were evaluated until complete healing or for 4 weeks, whichever occurred first. RESULTS: There were no significant differences between the four treatment groups with respect to times to full crusting; loss of vesicles, ulcers and crusts; cessation of new lesion formation; a 50% reduction in the area of affected skin; and the loss of acute pain. CONCLUSIONS: Famciclovir 750 mg once daily, 500 mg twice daily and 250 mg daily, and aciclovir 800 mg five times daily are three times comparable in efficacy with respect to the cutaneous healing of herpes zoster. The current study was not designed to assess the effects of the treatments on postherpetic neuralgia (PHN).     

A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma

To determine the efficacy of high doses of intravenous gammaglobulin (IVIG) for the treatment of severe, steroid-dependent asthma in patients between 6 and 68 years of age, a randomized, double-blind, placebo-controlled multicenter clinical trial was conducted in private and university hospitals in the United States. Patients were randomized to one of three treatment arms: 2 g IVIG/kg/month (16 patients); 1 g IVIG/kg/month (9 patients); or 2 g iv albumin (placebo)/kg/month (15 patients). The treatment consisted of seven monthly infusions followed by a posttreatment observation period. The primary outcome measurement was mean daily prednisone-equivalent dose requirements, determined during the observation month preceding initiation of treatment and compared to the month preceding the seventh infusion. Secondary clinical endpoints measured were pulmonary function, frequency of emergency room visits or hospitalizations, and number of days absent from school or work. When adjusted for body weight, the mean dose requirements fell by 33, 39, and 33% in the placebo, IVIG (1 g/kg), and IVIG (2 g/kg) treatment arms, respectively. The differences between therapies were not statistically different (P = 0.9728). The mean percentage-of-predicted FEV1 fell in all three treatment groups during the treatment period but there was no significant difference between treatment groups (P = 0.8291). There was also no significant difference in the percentage of subjects requiring emergency room visits or hospitalizations or missing days of work/school, among the three treatment groups. The trial was terminated prematurely after interim analysis determined the adverse experience rate was different between the three groups. Three patients, all randomized to the 2-g/kg IVIG dose group, were hospitalized with symptoms consistent with aseptic meningitis. In summary, in this randomized, double-blind, placebo-controlled multicenter study, high doses of IVIG did not demonstrate a clinically or statistically significant advantage over placebo (albumin) infusions for the treatment of corticosteroid-dependent asthma. Subgroup analysis failed to identify markers predicting responsiveness. High-dose IVIG can also be associated with a significant incidence of serious adverse events.     

Zinc gluconate lozenges for common cold. A double-blind clinical trial

In a double-blind clinical trial, a total of 463 volunteers were enrolled in a study designed to compare the effects of zinc gluconate lozenges (4.5 mg zinc) and a placebo for common cold. The tablets were to be taken every 1-1 1/2 waking hours at the first symptoms and for the following days until the common cold was over, but for no longer than 10 days. During the winter months of 1987 and 1988, 145 experienced a common cold and 130 completed the study. For final analysis, 61 patients in the zinc lozenge group and 69 patients in the placebo lozenge group were evaluated. Based on the patients' records the duration and severity of the common cold were compared. No statistically significant differences were found between the patient groups. Two recent studies using a five-time higher zinc dose per lozenge for common cold showed a significant, positive effect, but associated with frequent side-effects, first of all taste distortion. In the present study there was a weak tendency (not statistically significant, p = 0.12) towards more patients in the zinc lozenge group than in the placebo lozenge group reporting side-effects.     

Efficacy of intravenous citalopram compared with oral citalopram for severe depression. Safety and efficacy data from a double-blind, double-dummy trial

BACKGROUND: Intravenous administration is often beneficial in the treatment of severely depressed patients. It is mainly the tri- and tetracyclic antidepressant drugs that can be administered intravenously. However, these drugs have a less favourable safety profile than newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). Citalopram is the only SSRI that is available in a formulation for infusion. This double-blind, randomised, multicentre trial was designed to compare the efficacy and tolerability of citalopram infusion (40 mg per day) and citalopram tablet (40 mg per day). METHODS: Patients were randomised to receive either placebo tablet plus citalopram infusion (the infusion group; n=135) or citalopram tablet plus placebo infusion (the tablet group; n=119). After receiving randomised treatment for eight days, all patients entered an open treatment phase, during which they received oral citalopram 40 mg per day for five weeks. RESULTS: Although there was no difference in Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of the randomised treatment period, by the end of the open treatment phase the reduction in MADRS scores was significantly greater in the infusion group than in the tablet group (p=0.015). The infusion group also showed superior efficacy in Clinical Global Impressions assessments. Citalopram was equally well tolerated in both treatment groups. CONCLUSIONS: This trial confirmed the efficacy of citalopram 40 mg per day, and clearly supports the use of citalopram infusion in the treatment of severely depressed, hospitalised patients.     

阿坎酸治疗酒依赖的12周多中心随机双盲对照研究

目的:评价阿坎酸治疗酒依赖的疗效和安全性。方法:本研究采用随机、双盲、安慰剂对照的多中心临床试验设计。研究对象是符合美国精神障碍诊断与统计手册第4版(DSM-IV)酒依赖诊断标准的门诊或者住院患者。共入组230例,一组(n=116)用阿坎酸(体质量60 kg,1332 mg/d;≥60kg,1998 mg/d)治疗,另一组(n=114)接受安慰剂治疗,连续治疗12周。以累计戒酒天数(CAD)与校正累积戒酒持续时间(CCAD)、每次访视的复饮率、首次复饮时间作为评价疗效的主要指标。以饮酒次数、饮酒量、可视渴求量表评分、血γ-谷氨酰转移酶水平为评价疗效的次要指标。根据生命体征、实验室及心电图检查、不良事件报告评价安全性。结果:阿坎酸组与安慰剂组在累计戒酒天数[(43.7±34.7)d vs.(38.9±35.8)d]、校正累积戒酒持续时间[(52.0±41.3)%vs.(46.3±42.6)%]、每次访视的复饮率以及首次复饮时间分布等主要疗效评价指标均无统计学差异(均P0.05)。但在治疗12周后,阿坎酸组患者饮酒量的等级为戒除和小于5标准杯/d的比例(88.1%vs.78.7%)高于安慰剂组,可视渴求量表分[(2.6±2.3)vs.(3.3±2.9)]低于安慰剂组(均P0.05)。阿坎酸组和安慰剂组的不良事件发生率差异无统计学意义(22.6%vs.19.3%,P0.05)。阿坎酸组最常见的不良反应是腹泻和皮疹,与安慰剂组相比腹泻发生率(4.9%vs.3.2%)和皮疹发生率(3.9%vs.2.1%)无统计学差异(均P0.05)。结论:阿坎酸对减少酒依赖患者饮酒量、降低渴求等方面的疗效优于安慰剂,并且安全性良好。     

Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trial

BACKGROUND: Recently, fungal elements were suspected to be the causative agent of chronic rhinosinusitis, and benefits of topical amphotericin B therapy have been reported. OBJECTIVE: The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind, randomized clinical trial. METHODS: Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks. The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable. Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score. Before and after treatment, nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and standard culture techniques. RESULTS: Seventy-eight patients were included, and 60 patients finished the study per protocol. In the control group, no positive response (0 of 32) was observed, and 2 of 28 patients responded in the amphotericin B group (P>.2). The symptom scores were distinctly worse after amphotericin B therapy (P <.005). The other parameters investigated did not differ remarkably between the treatment groups. CONCLUSION: Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms.     

Clinical evaluation of ketotifen for chronic urticaria: multicenter double-blind comparative study with clemastine

A double-blind study was performed in 305 patients to compare ketotifen capsule and clemastine tablet. Ketotifen alleviated eruption and itching to a significantly greater extent than clemastine. The utility rating of ketotifen was significantly higher than that of clemastine.     

Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.     

Treatment of chronic oral candidiasis with clotrimazole troches. A controlled clinical trial.

Twenty patients with chronic oral candidiasis were assigned by random allocation to a two-week course of either 10-mg clotrimazole buccal troches or placebo taken five times daily in a double-blind clinical trial. Each of the 10 recipients of clotrimazole had marked regression of symptoms and mucosal lesions, and in nine patients potassium hydroxide preparations and cultures of mucosal scrapings gave no evidence of candidiasis. In contrast, only one of the 10 patients receiving placebo showed any improvement. The clinical outcome in the clotrimazole-treated group was significantly more favorable (P less than 0.001) than in the group receiving placebo. No adverse reactions to the drug were observed. After the blind phase of their trial, 15 patients were treated with clotrimazole troches in an open trial. One to three troches per day were found adequate to sustain remissions. We conclude that clotrimazole is highly effective treatment for chronic oral candidiasis.     

A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea

STUDY OBJECTIVES: To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure (CPAP) compared with conventional nasal interfaces. DESIGN: A randomized single-blind crossover study. SETTING: Hospital-based sleep laboratory. PATIENTS OR PARTICIPANTS: 21 CPAP-na?ve patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36) Interventions: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP titrations were undertaken at the start of each treatment arm. Outcome measures were recorded at baseline and at the end of each treatment arm. These included polysomnography variables, CPAP compliance, subjective sleepiness, obstructive sleep apnea symptom ratings, and adverse effects. There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06) or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7-2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [-5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and oral interfaces significantly improved polysomnographic variables, Epworth Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance from baseline (all P < 0.05). CONCLUSIONS: This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea. Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated.     

A double-blind comparison of nasal budesonide and oral astemizole for the treatment of perennial rhinitis

Sixty-nine outpatients with symptomatic perennial rhinitis were recruited to this double-blind, parallel-group study to compare budesonide nasal spray with oral astemizole. Following a 1-week run-in on placebo, 67 patients achieved a mean daily total symptom score of at least 4 (scoring for each symptom was 0 = none, 1 = mild, 2 = moderate, 3 = severe), and were randomized to study treatments - 33 to budesonide, 100 ug in each nostril morning and evening, and 34 to astemizole, one 10-mg tablet each morning, for a period of 4 weeks. No antihistamine preparations other than eye drops and no corticosteroids were permitted during the active treatment period. Patients recorded symptoms of blocked nose, runny nose, sneezing, itchy nose, sore eyes or runny eyes in diary cards each evening before retiring. Diary card data showed that there was significantly greater improvement in blocked nose, runny nose and runny eyes during the first 2 weeks of budesonide treatment than during the same period on astemizole. A similar, although non-significant, trend was observed for sneezing and itchy nose, but there was no apparent difference in the reporting of sore eyes. After 4 weeks, blocked nose and runny nose remained significantly less troublesome in the budesonide group. Both treatments were well-tolerated and no major adverse effects were reported. Patient ratings for treatment efficacy were significantly higher for budesonide than astemizole at both 2 weeks and 4 weeks.     

Suppression of frequently recurring genital herpes. A placebo-controlled double-blind trial of oral acyclovir

We studied 35 otherwise healthy adults with frequently recurring genital herpes (greater than or equal to 1 episode per month), in a double-blind trial comparing oral acyclovir with placebo capsules for suppression of recurrent infection. The patients were treated for 125 days unless herpes recurred. Among 32 evaluable patients, there were significantly fewer recurrences during acyclovir treatment (4 of 16) than during placebo treatment (16 of 16, P less than 0.001). The mean duration of therapy was significantly longer for patients receiving acyclovir than for those receiving placebo (114.9 vs. 24.8 days, P less than 0.001). Of 19 patients who had recurrences in the blind trial, only 2 had recurrences when given acyclovir in a second, open-study phase. All patients had recurrences after completing acyclovir treatment. The therapy was well tolerated, with minimal gastrointestinal upset and one hypersensitivity reaction. Studies of the viral isolates demonstrated that lesions developing in patients receiving acyclovir contained drug-resistant virus. Later recurrences in these patients were associated with drug-sensitive virus. We conclude that oral acyclovir suppresses genital herpes in patients with frequent recurrences, but the potential for problems with drug resistance and the long-term safety need to be more fully explored.     

Endometrial patterns during therapy with danazol or gestrinone for endometriosis: structural and ultrastructural study.

We treated 36 women with laparoscopically proven endometriosis with danazol 600 mg/d (n = 17) or gestrinone 5.0 mg/wk (n = 19) for 6 months. Endometrial samples were obtained before and at 3 and 6 months of treatment and were studied by light, scanning, and transmission electron microscopy. At 3 months of treatment, the endometria of the danazol-treated patients were more atrophic than those of the women who received gestrinone. Some cell organelle involution was evident in patients of both treatment groups. After 6 months of treatment, marked endometrial atrophy was observed in all the patients, including those in whom spotting had occurred. The ultrastructural investigation demonstrated complete involution of the cytoplasmic organelles with cytoplasmic collapse in glandular cells of patients treated with danazol, whereas in the gestrinone group degeneration phenomena were observed in both nucleus and cytoplasm. Irregular secretory transformation was seen in the endometria of patients in both groups. Long-term treatment with danazol caused endometrial atrophy similar to that induced by gestrinone, but it appeared earlier; thus, the former drug seems preferable in short-term treatment.     

Endocrinology: A prospective randomized single-blind comparative trial of nafarelin acetate with buserelin in long-protocol gonadotrophin-releasing hormone analogue controlled in-vitro fertilization cycles

The use of gonadotrophin-releasing hormone (GnRH) agonists tocontrol ovulation induction cycles for in-vitro fertilization(IVF) has been shown to increase the pregnancy rate and livebirth rate compared with non-analogue cycles. Different formulationsof GnRH agonist are available with different routes and frequenciesof administration. In this prospective study, the efficacy andsafety of intranasal nafarelin and buserelin as adjunctive therapyduring IVF were assessed. A total of 240 female patients wererecruited to the study and in the first phase patients wererandomized to receive either intranasal nafarelin 200 µgtwice daily or buserelin 200 µg five times daily. In thesecond phase, patients received either nafarelin 400 µgtwice daily or buserelin 200 µg five times daily. Nafarelin400 µg and buserelin 200 µg both produced clinicalpregnancy rates of 31% per recruit and 39% per embryo transfer.The rates for nafarelin 200 ug were 23 and 37% respectively.There was no statistically significant difference in pregnancyrates, by either drug or dosage. The time taken for pituitarydown-regulation to be achieved was significantly longer on nafarelin200 µg than on either nafarelin 400 µg or buserelin.The total number of days stimulation with human menopausal gonadotrophinrequired to reach criteria for human chorionic gonadotrophin(HCG) administration was significantly longer on buserelin thanon either dose of nafarelin. Median serum oestradiol concentrationson the day of HCG administration were significantly higher oneither dose of nafarelin than on buserelin.     

Multicenter,randomized, double-blind,placebo-controlled clinical trial of vital wheat gluten oral immunotherapy

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