Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study

BACKGROUND: In a recent study, we showed that intranasal capsaicin spray gives a significant and long-term reduction of symptoms in nonallergic noninfectious perennial rhinitis patients. However, in daily practice, the studied application regimen proved to be impractical because of the large number of visits required in a short period of time. In the present study, we conducted a double-blind double-dummy parallel groups trial to determine whether a more practical capsaicin application schedule is equally effective. METHODS: Thirty patients were randomized into two different treatment regimens: one group received capsaicin five times on the first day at 1-h intervals. This was followed by a placebo dummy once every second or third day for a total of five treatments 2 weeks after the capsaicin application (group A). The other group (B) received the placebo dummy five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. RESULTS: The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in safety data (smell, blood pressure, heart rate) were found. CONCLUSIONS: We conclude that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.     

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials

Rationale: Several randomized, double‐blind, placebo‐controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta‐analysis to determine the overall treatment effect. Methods: A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double‐blind, placebo‐controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non‐nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta‐analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software. Data synthesis: Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD ?0.49, 95% CI: ?0.60 to ?0.38; P < 0.00001; I² = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (?0.41; 95% CI: ?0.56 to ?0.27), rhinorrhoea (?0.44; 95% CI: ?0.66 to ?0.21), sneezing (?0.40; 95% CI: ?0.57 to ?0.23) and nasal itching (?0.39; 95% CI: ?0.53 to ?0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (?0.30; 95% CI: ?0.43 to ?0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81–1.20; P = 0.91). Conclusions: This meta‐analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.     

Ineffectiveness of kallikrein in treatment of idiopathic male infertility: a double-blind, randomized, placebo-controlled trial

In order to clarify the potential of kallikrein for treatmentof idiopathic male infertility, a double-blind, randomized,placebo-controlled study was performed. A total of 44 patientswere treated with 600 IU/day kallikrein and 47 patients withplacebo for 12 weeks. Following two basal investigations, controlexaminations were performed at 6 and 12 weeks and included conventionaland computer-aided semen analysis, hormone measurements andevalution of drug safety. No significant changes in sperm concentration,normal sperm morphology and sperm motility evaluated by conventionalanalysis were detected. Computer-aided semen analysis revealeda significant increase in average path velocity and lateralhead displacement of spermatozoa only in the placebo group.Within the observation period of 6 months four pregnancies occurredin each group. In conclusion, kallikrein treatment at a doseof 600 IU/day leads neither to an improvement of semen variablesnor does it increase the pregnancy rate of the female partners,and is therefore not suited for therapy of idiopathic male infertility.     

Multicenter, double-blind, placebo-controlled trial of triamcinolone acetonide nasal aerosol in the treatment of perennial allergic rhinitis

In a double-blind study involving 205 patients with perennial allergic rhinitis, statistically significantly greater symptomatic improvements were evident following the administration of 200 micrograms/day triamcinolone acetonide aerosol than following placebo. These improvements were evident as early as week 1 and were sustained throughout the 12-week study. They were accompanied by greater reductions in nasal eosinophils. Triamcinolone acetonide aerosol was well tolerated and had no effect on serum cortisol levels.     

A 300 IR sublingual tablet is an effective,safe treatment for house dust mite–induced allergic rhinitis: An international,double-blind,placebo-controlled,randomized phase III clinical trial

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Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial

BACKGROUND: Nasal challenge studies have suggested histamine and cysteinyl leukotrienes are important proinflammatory mediators in allergic rhinitis. This study was designed to determine the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist, administered alone or concomitantly with loratadine, an H(1)-receptor antagonist, in seasonal allergic rhinitis. OBJECTIVE: The purpose of this study was to determine the effect of concomitant use of montelukast and loratadine in the treatment of seasonal allergic rhinitis. METHODS: In this multicenter (N = 12) double-blind, randomized, parallel-group, placebo-controlled 2-week trial, 460 men and women, aged 15 to 75 years, with spring seasonal allergic rhinitis were randomly allocated to receive 1 of the following 5 treatments: montelukast 10 or 20 mg, loratadine 10 mg, montelukast 10 mg with loratadine 10 mg, or placebo, once daily in the evening. The primary end point was daytime nasal symptoms score (average of congestion, rhinorrhea, itching, and sneezing). Other end points were eye symptoms, nighttime symptoms, individual daytime nasal symptoms, global evaluations (patient's and physician's), and rhinoconjunctivitis quality-of-life scores. RESULTS: Concomitant montelukast with loratadine improved the primary end point significantly (P <.001) compared with placebo and each agent alone. Compared with placebo, montelukast with loratadine also significantly improved eye symptoms, nighttime symptoms, individual daytime nasal symptoms, global evaluations, and quality of life. Montelukast alone and loratadine alone caused modest improvements in rhinitis end points. All treatments were similarly well tolerated. CONCLUSIONS: Concomitant montelukast with loratadine provided effective treatment for seasonal allergic rhinitis and associated eye symptoms with a safety profile comparable with placebo.     

Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial

To examine the role of recombinant human follicle stimulating hormone (rhFSH) in male idiopathic infertility a randomized, double-blind, placebo-controlled study was performed. Of 211 patients screened, 67 were finally included. After two pre-examinations, patients were randomized and treated for 12 weeks, either with 150 IU rhFSH or with placebo. Examinations (physical examination, scrotal ultrasonography, semen analysis, hormone measurements, and in 31 patients electron microscopy (EM) of spermatozoa were performed 6 and 12 weeks after treatment initiation and 6 and 12 weeks after completion of treatment. Pregnancies were recorded for a further 3 months after the last examination. Of the 67 patients included in the study, 34 treated and 31 placebo patients could be analysed. In the treated group, FSH was elevated compared to baseline values (P < 0.001). At the end of treatment testicular volume in the treated group was increased compared to placebo (P < 0.05) and baseline (P < 0.001). Apart from an increase in sperm motility (P < 0.05) in the placebo group and in sperm DNA condensation (P < 0.001) in the treated group no significant changes were observed in semen parameters. Two spontaneous pregnancies in partners of men in the treated group and none in the placebo group occurred. However, two pregnancies occurred in partners of men in the placebo group induced by intrauterine insemination or intracytoplasmic sperm injection. In conclusion, at the chosen dose and duration, rhFSH did not lead to an improvement of conventional or EM sperm parameters nor to an increase in pregnancy rates. However, the increased testicular volume and sperm DNA condensation give reason for further investigations.      

Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring

BACKGROUND: Cysteinyl leukotrienes are important proinflammatory mediators believed to have a role in allergic rhinitis. OBJECTIVE: This multicentre, randomized, double-blind, placebo- and active-controlled trial evaluated the effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, for treating patients with seasonal allergic rhinitis. METHODS: After a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients (aged 15-81 years) with active allergic rhinitis symptoms were randomly assigned to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n = 352) administered once daily at bedtime for 2 weeks during the spring allergy season. RESULTS: Mean patient characteristics and symptom scores at baseline were similar for the three treatment groups. The primary end-point, daytime nasal symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and sneezing scores; 0-3 scale), improved from baseline during treatment by (least squares mean, 95% confidence interval) - 0.37 (- 0.43, - 0.31), - 0.47 (- 0.52, - 0.43), and - 0.24 (- 0.29, - 0.18) in the montelukast, loratadine, and placebo groups, respectively (P < or = 0.001 comparing each active treatment with placebo). Mean changes from baseline in all other diary-based scores, including night-time and eye symptom scores, were significantly greater for each active treatment than for placebo. The rhinoconjunctivitis quality of life overall score improved significantly with montelukast and with loratadine as compared with placebo. Montelukast and loratadine showed a safety profile comparable to that of placebo. CONCLUSION: Montelukast is well tolerated and provides improvements in daytime and night-time symptoms, as well as quality of life parameters, for patients with seasonal allergic rhinitis.     

Effects of probiotics on allergic rhinitis induced by Japanese cedar pollen: randomized double-blind, placebo-controlled clinical trial

BACKGROUND: Lactobacillus casei strain Shirota (LcS) has been found to exert antiallergic effects in animal experiments, but there is little information about its clinical effects in human patients with allergy. METHODS: We performed a randomized double-blind, placebo-controlled study to investigate the effects of LcS in patients with allergic rhinitis triggered by Japanese cedar pollen (JCP). Participants were asked to drink fermented milk containing LcS (LcS group) or placebo (control group) for 8 weeks. Clinical symptoms and immunological parameters were compared between the two groups. RESULTS: Symptom-medication scores (SMS) worsened in accordance with the increase in the amount of scattered JCP. In terms of the nasal and ocular SMS, there was no significant difference between the LcS group and the placebo group during the ingestion period. In the subgroup of patients with moderate-to-severe nasal symptom scores before starting the ingestion of test samples, supplementation with LcS tended to reduce nasal SMS. CONCLUSION: These results indicate that fermented milk containing LcS does not prevent allergic symptoms in patients sensitive to JCP, but may delay the occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom scores.     

Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study

BACKGROUND: There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases. OBJECTIVE: The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. METHODS: A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared. RESULTS: Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators. CONCLUSION: A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.     

Once-daily mometasone furcate aqueous nasal spray (Nasonex™) in seasonal allergic rhinitis: an active- and placebo-controlled study

Mometasone furoate aqueous nasal spray (Nasonex™) was compared with beclomethasone dipropionate (BDP) aqueous nasal spray in a double-blind, randomized, placebo-controlled, double-dummy, parallel-group study of adults with moderate to severe seasonal allergic rhinitis. Patients allergic to at least one tree and/or grass aeroallergen received one of the following regimens for up to 4 weeks: mometasone furoate 100 μg once daily [OD] ( n = 126) or 200 μg OD ( n = 126), BDP 200 μg twice daily ( n = 126), or only placebo spray ( n = 123). Physician-rated nasal and total symptom scores, and global evaluation of overall condition and therapeutic response by physicians and patients, showed that the three active treatments were equally effective, and all three were significantly superior to placebo at most time points. Overall, mometasone furoate 200 μg OD demonstrated somewhat greater numerical, but not statistical, superiority to mometasone furoate 100 μg OD at the earliest evaluation time point. At the end of treatment, complete or marked relief was obtained in 77% of patients with mometasone furoate 100 μg/day, 79% with mometasone furoate 200 μg/day, and 74% with BDP, compared with 54% of placebo vehicle control patients. Mometasone furoate and BDP were equally well tolerated. It was concluded that mometasone furoate adequately controls symptoms of moderate to severe seasonal allergic rhinitis, offers the advantage of OD treatment, and is well tolerated.     

The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized,double-blind,placebo-controlled phase III trial

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Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre study

BACKGROUND: Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. OBJECTIVE: To study rupatadine efficacy and safety for moderate to severe CIU treatment. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. RESULTS: A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. CONCLUSION: Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU.     

Once-daily fexofenadine treatment for chronic idiopathic urticaria: a multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Chronic idiopathic urticaria (CIU) can have a profound effect on patients' health and quality of life. OBJECTIVE: To evaluate the efficacy and safety of once-daily dosing of fexofenadine hydrochloride, 180 mg, on CIU. METHODS: This randomized, double-blind, parallel-group, placebo-controlled study consisted of a placebo run-in period followed by a 4-week treatment period. Patients 12 years and older with active CIU were randomized 2:1 to receive once-daily fexofenadine, 180 mg, or placebo. The primary end points were change from baseline in mean daily number of wheals (MNW score) and mean daily severity of pruritus during treatment. Secondary efficacy measures included modified total symptom scores and MNW and pruritus severity scores evaluated weekly and instantaneously at trough drug levels. RESULTS: Patients administered fexofenadine (n = 163) experienced significantly greater improvements in MNW and pruritus severity scores compared with the placebo group (n = 92) (P < .001 for both). Similarly, throughout treatment and at each individual week, the mean reductions in modified total symptom scores were significantly greater in the fexofenadine group (P < or = .005 for all comparisons vs placebo). The mean reductions in instantaneous MNW and pruritus severity scores were greater in patients in the fexofenadine group than in those who received placebo (MNW score: P = .015; pruritus severity score: P < .001). There were no significant differences in the frequency of treatment-emergent adverse events between the 2 treatment groups. CONCLUSIONS: A once-daily dose of fexofenadine hydrochloride, 180 mg, offered effective, well-tolerated relief for the management of CIU.     

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.