Identifying in-market application of Pelargonium root extract EPs 7630 for the treatment of COVID-19: analysis of pharmacovigilance data.

Introduction: Phytopharmaceutical products are successfully used for acute respiratory infections and may therefore be promising candidates for adjuvant symptomatic treatment of COVID-19. In vitro and clinical studies suggest that the proprietary Pelargonium sidoides DC. root extract EPs 7630 has antiviral and immunomodulatory properties, and effects on SARS-CoV-2 propagation have been shown in vitro. Medicinal products containing the extract have been approved for the symptomatic treatment of acute viral respiratory tract infections. Methods: We present a retrospective review of case reports submitted spontaneously to the pharmacovigilance database of the manufacturer of EPs 7630 and containing information on the off-label use of the extract for the treatment and prophylaxis of COVID-19 and of post-COVID-19 syndrome. Eligible case reports were identified by automated database searches. Results: Forty-four case reports filed between December 2019 and February 2023 were eligible for analysis. More than ¾ described the use of EPs 7630 for treatment of COVID-19 while the remaining reports referred to the treatment of post-COVID-19 syndrome or to COVID-19 prophylaxis. 15/22 cases which reported on treatment duration indicated an intake of EPs 7630 for up to 7 days. Five case reports indicated the use of EPs 7630 as COVID-19 monotherapy while 14 indicated a combination treatment with other drugs. All 28 cases that reported on treatment outcome characterized the patients as improved. Thirty case reports (68%) did not indicate any complications. The most frequent suspected adverse reactions were gastrointestinal complaints and hypersensitivity reactions, both of which may occur as known adverse effects of EPs 7630. No unexpected adverse reactions were observed. Conclusion: Reported cases confirm that there was a certain off-label use of EPs 7630 for COVID-19 in the market. Even though no formal conclusions about the efficacy of EPs 7630 in COVID-19 can be drawn, a beneficial effect would be explainable by the pharmacological profile of the extract. Further assessment of the effects of EPs 7630 in COVID-19-related indications therefore appears to be both justified and promising, particularly as the available case reports did not give rise to any safety concerns also in this patient group.

Effects of EPs 7630 on the duration of inability to work in acute bronchitis - a meta-analysis.

Background: Acute bronchitis (AB) has an enormous economic impact through lost working time. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce the time of inability to work. Methods: A meta-analysis of double-blind, randomized, placebo-controlled trials with adult patients suffering from AB was performed. The average number of days of inability to work and the proportion of patients who were still unable to work after one week's treatment were assessed. Results: Four clinical trials with a total of 1,011 evaluable patients who received the marketed dosage of EPs 7630 (n=505) or placebo (n=506) for seven days were included in the meta-analysis. At baseline, 845/1,011 patients (83.6%) were unable to work. In the four trials, the proportion decreased to between 19 and 14% for EPs 7630 and to between 41 and 55% for placebo (meta-analysis risk ratio and 95% confidence interval: 0.35; 0.26-0.45; p<0.001). For the number of sick days, a weighted mean difference of 1.73 days (1.17-2.29 days; p<0.001) favoring EPs 7630 was observed. Conclusions: For adults suffering from AB, this meta-analysis demonstrates that seven days' treatment with Pelargonium sidoides extract EPs 7630 significantly reduces the average number of sick days and significantly increases the proportion of patients who are able to return to work.

Safety of Pelargonium extract EPs 7630 in young children with acute bronchitis.

Background: The efficacy and tolerability of Pelargonium sidoides DC. root extract EPs 7630 in children with acute bronchitis (AB) have been widely demonstrated. We investigated the safety and tolerability of a syrup formulation and an oral solution in pre-school children. Methods: In an open-label, randomized clinical trial (EudraCT number 2011-002652-14), children aged 1-5 years suffering from AB received EPs 7630 syrup or solution for 7 days. Safety was assessed by frequency, severity, and nature of adverse events (AE), vital signs, and laboratory values. Outcome measures for evaluating the health status were the intensity of coughing, pulmonary rales, and dyspnea, measured by the short version of the Bronchitis Severity Scale (BSS-ped), further symptoms of the respiratory infection, general health status according to the Integrative Medicine Outcomes Scale (IMOS), and satisfaction with treatment according to the Integrative Medicine Patient Satisfaction Scale (IMPSS). Results: 591 children were randomized and treated with syrup (n = 403) or solution (n = 188) for 7 days. In both treatment groups, the number of adverse events was similarly low and revealed no safety concerns. The most frequently observed events were infections (syrup: 7.2%; solution: 7.4%) or gastrointestinal disorders (syrup: 2.7%; solution: 3.2%). After one week's treatment, more than 90% of the children experienced an improvement or remission of the symptoms of the BSS-ped. Further respiratory symptoms decreased similarly in both groups. At Day 7, more than 80% of the whole study population had completely recovered or showed a major improvement as assessed by the investigator and the proxy, respectively. Parents were "very satisfied" or "satisfied" with the treatment in 86.1% of patients in the combined syrup and solution group. Conclusion: Both pharmaceutical forms, EPs 7630 syrup and oral solution, were shown to be equally safe and well tolerated in pre-school children suffering from AB. Improvement of health status and of complaints were similar in both groups.

Effects of Pelargonium sidoides extract EPs 7630 on acute cough and quality of life - a meta-analysis of randomized, placebo-controlled trials.

Background: Cough is a leading symptom of viral acute respiratory infections such as acute bronchitis (AB) and the common cold (CC), which can be debilitating and may persist for several weeks. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce cough and improve disease-related quality of life (QoL). Methods: We performed a meta-analysis of randomized, placebo-controlled trials investigating the efficacy of EPs 7630 in AB or CC. Efficacy analyses included change from baseline in a cough intensity score, remission of cough, and disease-associated impairments of QoL. Results: Data of 2,195 participants from 11 trials (3 in children/adolescents with AB, 3 in adults with AB, 5 in adults with CC) were eligible. In children/adolescents with AB, 79.6% of participants treated with EPs 7630 and 41% treated with placebo showed a reduction in the intensity of cough by at least 50% of baseline values at day 7 [meta-analysis rate/risk ratio (RR), EPs 7630 / placebo: 1.86 (95% CI: 1.34; 2.95)], and 18.0% vs 5.5% presented with complete remission of cough [RR: 2.91 (95% CI: 1.26; 6.72)]. In adults with AB, 88.7% of participants in the EPs 7630 group and 47.6% in the placebo group showed a ≥50% response for cough intensity [RR: 2.13 (95% CI: 1.37; 3.31)], while 26.0% vs 6.3% did not cough any more at day 7 [RR: 5.00 [95% CI: 3.10; 8.07)]. Cough scale results were supported by significant improvements over placebo in the pursuit of normal daily activities and other QoL measures. In CC, 56.8% of participants treated with EPs 7630 and 38.8% treated with placebo showed a ≥50% cough intensity reduction [RR: 1.40 (95% CI: 1.19; 1.65)] at day 5, while 26.1% versus 18.4% showed complete remission of cough for EPs 7630 and placebo, respectively [RR: 1.40 (95% CI: 1.06; 1.84)]. CCassociated pain/discomfort and impairment of usual activities were no longer present in 41.5% and 48.8% of participants treated with EPs 7630 compared to less than 40% of patients in the placebo group. Conclusions: The results show that EPs 7630 reduces the burden and leads to earlier remission of cough. Advantages for EPs 7630 were also reflected in self-rated measures of disease-associated QoL. Of note, patients treated with the herbal product felt able to resume their usual daily activities sooner.

Pelargonium Extract EPs 7630 in the Treatment of Human Corona Virus-Associated Acute Respiratory Tract Infections - A Secondary Subgroup-Analysis of an Open-Label, Uncontrolled Clinical Trial.

Background: Experience in treating human coronavirus (HCoV) infections might help to identify effective compounds against novel coronaviruses. We therefore performed a secondary subgroup-analysis of data from an open-label, uncontrolled clinical trial published in 2015 investigating the proanthocyanidin-rich Pelargonium sidoides extract EPs 7630 in patients with the common cold. Methods: 120 patients with common cold and at least 2 out of 10 common cold symptoms received one film-coated 20 mg tablet EPs 7630 thrice daily for 10 days in an uncontrolled, interventional multicentre trial (ISRCTN65790556). At baseline, viral nucleic acids were detected by polymerase chain reaction. Common cold-associated symptoms and treatment satisfaction were evaluated after 5 days and at treatment end. Based on the data of patients with proof of viral nucleic acids, we compared the course of the disease in patients with or without HCoV infection. Results: In 61 patients, viral nucleic acids were detected. Of these, 23 (37.7%) were tested positive for at least one HCoV (HCoV subset) and 38 (62.3%) for other viruses only (non-HCoV subset). Patients of both subsets showed a significant improvement of common cold symptoms already after 5 days of treatment, although the observed change tended to be more pronounced in the HCoV subset. At treatment end, more than 80% of patients of both groups were completely recovered or majorly improved. In both subsets, less than 22% of patients took concomitant paracetamol for antipyresis. The mean number of patients' days off work or school/college was similar (0.9 ± 2.6 days in HCoV subset vs 1.3 ± 2.8 days in non-HCoV subset). In both groups, most patients were satisfied or very satisfied with EPs 7630 treatment. Conclusion: EPs 7630 treatment outcomes of common cold patients with confirmed HCoV infection were as favourable as in patients with other viral infections. As this trial was conducted before the pandemic, there is currently no evidence from clinical trials for the efficacy of EPs 7630 in patients with SARS-CoV-2 infection. Dedicated non-clinical studies and clinical trials are required to elucidate the potential of EPs 7630 in the early treatment of HCoV infections.

WS PRO 160 I 120 mg (a combination of sabal and urtica extract) in patients with LUTS related to BPH.

INTRODUCTION: Lower urinary tract symptoms (LUTS) caused by prostatic enlargement are a common impairing condition in men aged 50 years and older. In the management of LUTS related to benign prostatic hyperplasia (BPH), medication, particularly by α-adrenoceptor antagonists, 5α-reductase inhibitors, and phytopharmaceuticals, is considered the first-line therapy. Despite their popularity, a number of adverse effects on the cardiovascular or cognitive systems have been reported for some of the synthetic drugs. One of the promising herbal preparations for the treatment of patients suffering from LUTS related to BPH is WS PRO 160 I 120 mg, a combination of sabal fruit extract and urtica root extract. METHODS: This review of the literature summarizes clinical evidence for WS PRO 160 I 120 mg derived from four randomized placebo- or reference-controlled double-blind clinical trials including men aged 50 years and older. In all trials, symptomatic improvement was evaluated by the International Prostate Symptom Score (I-PSS) total score. RESULTS: Treatment effects of WS PRO 160 I 120 mg were shown to be superior over placebo and comparable with the 5α-reductase inhibitor finasteride or the α1-adrenoceptor antagonist tamsulosin with more favorable tolerability and safety profiles as compared with the reference drugs. CONCLUSIONS: The results suggest WS PRO 160 I 120 mg to be considered as a valid alternative in the treatment of patients with early BPH, especially with view to sexual function and a good quality of life, especially in long-term use.

Treatment with EPs 7630, a Pelargonium Sidoides Root Extract, Is Effective and Safe in Patients with the Common Cold: Results From a Randomized, Double Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: EPs 7630 was shown to be effective and safe in the treatment of acute respiratory tract infections such as acute bronchitis, acute rhinosinusitis, and acute tonsillopharyngitis. A clinical trial was conducted to investigate its efficacy and safety in the common cold. METHODS: In this multicenter, randomized, double-blind phase 3 clinical trial, 105 adults suffering from common cold symptoms were randomized to a thrice-daily administration of either 1 film-coated tablet containing 40 mg EPs 7630 or matched placebo for a treatment period of 10 days. The primary outcome measure was the sum of differences in the cold intensity score (CIS) from day 1 to day 5, defined as the Sum of the Symptom Intensity Differences (SSID), indicating the degree of symptom improvement in the course of 5 days of treatment. Among the secondary outcomes were clinical cure defined as (a) complete resolution of all cold symptoms (CIS = 0 points) or (b) complete resolution of all or all but one cold symptom, treatment outcome, satisfaction with treatment, and safety parameters. RESULTS: On day 5, the mean (±SD) SSID was significantly higher in the EPs 7630 group compared with the placebo group (12.5 ± 4.4 points versus 8.8 ± 6.8 points). Moreover, 55% of patients in the EPs 7630 group rated the treatment outcome as at least "major improvement" compared with 15% of patients in the placebo group. On day 10, 45% of patients of the EPs 7630 group and 12% of patients of the placebo group had reached 0 points on the CIS (=clinical cure, definition a), whereas all or all but one symptom (clinical cure, definition b) had completely resolved in 74% (EPs 7630) and 25% of patients (placebo), respectively. Satisfaction with treatment was higher in the EPs 7630 than in the placebo group (75% vs 37%) (P values ≤ .0002). During the clinical trial, adverse events occurred in 5 patients (9.4%) in the EPs 7630 and in 7 (13.5%) in the placebo group. All adverse events were of mild intensity, with the exception of 3 events in the placebo group, which were classified as moderate. CONCLUSIONS: Treatment with EPs 7630 was shown to be superior to placebo in patients with the common cold indicating faster reduction of symptom intensity and distinctly more pronounced effects achieved by administration of the investigational drug in patients suffering from the common cold. Results extend previous findings on efficacy, safety, and tolerability of this active substance.

SAFETY AND EFFECTS OF CRATAEGUS EXTRACT WS 1442 AND NORDIC WALKING ON LIPID PROFILE AND ENDOTHELIAL FUNCTION: A RANDOMIZED, PARTIALLY BLINDED PILOT STUDY IN OVERWEIGHT VOLUNTEERS.

Overweight and physical inactivity adversely affect endothelial function and are risk factors for atherosclerosis and cardiovascular disease. Both Crataegus extract WS 1442 and physical exercise exert beneficial effects on endothelial function. We investigated whether WS 1442 and Nordic walking (NW) had comparable effects on endothelial function and lipid profile in overweight subjects. In this partially blinded pilot study, overweight, otherwise healthy volunteers aged 45-75 years were randomized into four groups as follows: WS 1442 2x450 mg/day (WS-standard), WS 1442 2x900 mg/day (WS-double), exercise 2x30 minutes/week (NW-low), and exercise 4x45 minutes/week (NW-high) for 12 weeks. Safety was assessed based on adverse events. Endothelial function testing (EndoPAT®), assessment of endothelial progenitor cells, lipid profiles, and treadmill testing were performed. Sixty subjects participated in the study. At baseline, subjects in WS-standard/-double groups had higher lipid levels and greater impairment of endothelial function. Subjects with impaired endothelial function showed improvement regardless of the type of intervention. Subjects in WS-standard and WS-double groups showed a trend towards modest decrease in triglycerides and modest increase in HDL-cholesterol; most changes were within the normal limits. In NW-low/-high groups, values also remained within the normal range. Exercise capacity improved in both NW groups. WS-double showed no additional benefits over WS-standard. All adverse events were unrelated or improbably related to treatment. In conclusion, WS 1442 and exercise training were safe and showed beneficial effects on endothelial function and lipid profile in overweight but otherwise healthy volunteers; exercise capacity improved only by Nordic walking.

Efficacy and Tolerability of High-dose Pelargonium Extract in Patients With the Common Cold.

Context • The common cold (CC) is usually caused by a viral infection. Antibiotics are often prescribed unnecessarily for it, although no evidence exists for any benefit in the CC. Effective alternatives are needed. Objective • The study intended to evaluate the efficacy of 7630, a proprietary extract of Pelargonium sidoides, the active ingredient in umckaloabo, compared with a placebo for the treatment of the CC. Design • This was a prospective, double-blind, parallel-group, placebo-controlled, phase 3 clinical trial (RCT), with an adaptive group-sequential design with 2 parts, both of which were 2-arm trials. The first used a standard dose (SD) of 3 × 30 drops per day of the active medication and the second used a high dose (HD) of 3 × 60 drops per day of the active medication, against 3 × 30 drops per day and 3 × 60 drops per day of a placebo, respectively. Setting • The study took place in 8 outpatient departments affiliated with hospitals. Participants • For the entire study, 207 adults with predefined cold symptoms that had been present for 24 to 48 h prior were included in the study, with 103 participating in the SD part and 104 participating in the HD part. Intervention • In the HD part, as covered in this article, the intervention group received treatment with 3 × 60 drops per day of the active medication and the control group received a placebo (control group), for a maximum period of 10 d. Outcome Measures • The primary outcome measure was the sum of differences in the cold intensity score (CIS) from day 1 to day 3 and from day 1 to day 5, defined as the sum of the symptom intensity differences (SSID). The criteria for the secondary outcome, efficacy, were (1) diverse response criteria according to the total CIS; (2) changes in individual CIS symptoms; (3) changes in further cold-relevant symptoms; (4) ability to work; (5) activity level; (6) general well-being; (7) health-related quality of life-the EuroQol questionnaire with 5 dimensions (EQ-5D), including the visual analogue scale EQ-VAS; (8) time until onset of treatment effect; (9) treatment outcome; and (10) satisfaction with treatment. Results • From baseline to day 5, the mean CIS decreased by 11.2 ± 4.8 points for the 7630 group and 6.3 ± 4.7 points for the control group. The mean SSID was 16.0 ± 7.6 points for the control group (P < .0001). After 10 d, 90.4% of the group receiving the active medication and 21.2% of the control group were clinically cured (P < .0001). In the treatment group, participants' inability to work was significantly lower, with a mean duration of 6.4 ± 1.6 d vs 8.3 ± 2.1 d for the control group (P < .0001), and treatment outcome-complete recovery or major improvement-was significantly better at day 5 for the active treatment group compared with the control group (P < .0001). Mild-to-moderate adverse events-all nonserious-occurred in 15.4% of those receiving active treatment vs in 5.8% for the control group. Conclusions • The active medication is an effective, well tolerated, and safe treatment for the CC. It significantly reduces the severity of symptoms and shortens the duration of the disease.

Pelargonium sidoides preparation EPs 7630 in COPD: health-related quality-of-life and other patient-reported outcomes in adults receiving add-on therapy.

OBJECTIVE: Patient-reported outcomes (PRO) such as health-related quality-of-life (HRQoL) belong to the most important criteria for the evaluation of medical therapies in clinical trials or practice-based benefit assessments. This study, therefore, revisited results of an earlier published clinical trial investigating the effects of the herbal drug preparation from the roots of Pelargonium sidoides EPs 7630, administered as add-on therapy in patients suffering from chronic obstructive pulmonary disease (COPD), with respect to HRQoL and other PRO. METHODS: A total of 199 adults diagnosed with COPD stages II/III and receiving standard treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were randomly assigned to add-on therapy with EPs 7630 or placebo for 24 weeks. HRQoL (disease-specific St. George's Respiratory Questionnaire, SGRQ; current HRQoL state according to the EuroQuol visual analog scale, EQ VAS) and PRO (Integrative Medicine Outcomes Scale, IMOS; Integrative Medicine Patient Satisfaction Scale, IMPSS; symptom severity score of cough, sputum production and sternal pain while coughing; duration of inability to work) were assessed at each study visit or documented daily by the patient in a patient diary, respectively. RESULTS: At week 24, all HRQoL and PRO measures showed a more pronounced improvement under EPs 7630 than under placebo (EQ VAS, p < .001; SGRQ total score, p < .001; symptom severity score of cough, sputum production, and sternal pain while coughing, p = .021; duration of inability to work, p = .004; two-sided t-test each; IMOS, p < .001, IMPSS, p < .001, two-sided Mantel-Haenszel test each). Moreover, the difference seen for the SGRQ exceeded the SGRQ minimal clinically important difference (MCID) threshold of 4 points. CONCLUSIONS: Add-on therapy with EPs 7630 led to an improvement in HRQoL and other PRO in adult patients with COPD compared to placebo while showing a good long-term tolerability.

EPs 7630 is effective and safe in children under 6 years with acute respiratory tract infections: clinical studies revisited.

OBJECTIVE: Pelargonium sidoides preparation EPs 7630 has been proven safe and effective in acute respiratory tract infections (aRTIs), but data for young children have not been presented separately. This study reviewed clinical studies and presents an overview of known and newly analyzed data from children <6 years. METHODS: MEDLINE and EMBASE were searched for interventional and non-interventional studies which investigated the effects of EPs 7630 in aRTIs and included children <6 years of age. Sub-group analyses for this age range were performed for symptom scales, global efficacy or effectiveness assessments, and safety outcomes. RESULTS: Seven studies with 1067 children <6 years exposed to EPs 7630 were identified. Efficacy of EPs 7630 was significantly superior to placebo in reducing symptom intensity and time until complete recovery in two randomized, double-blind trials in patients with acute bronchitis (AB). Similar symptom time courses were observed in two non-comparative observational studies in AB. One non-comparative, open-label study was identified in acute tonsillopharyngitis (ATP), and one in acute rhinosinusitis (ARS). In both indications, nearly all children showed complete recovery or major symptom improvements during the treatment period, with changes that were similar to those observed in controlled trials investigating older patient populations. The results were supported by an additional observational study including children with various diagnoses of aRTIs. EPs 7630 was safe and well-tolerated. CONCLUSIONS: EPs 7630 is efficacious in children <6 years suffering from AB. The analyses also support the effectiveness of the product in ATP and in ARS. No safety concerns were identified.

[Pelargonium sidoides in acute bronchitis - Health-related quality of life and patient-reported outcome in adults receiving EPs 7630 treatment]. / Pelargonium sidoides bei akuter Bronchitis - Gesundheitsbezogene Lebensqualität und Therapiebeurteilung aus Patientensicht unter Behandlung mit EPs 7630.

Health-related quality of life (HRQL) and patient-reported outcome (PRO) have become important outcome parameters for the evaluation of medical treatment within clinical trials and, furthermore, to evaluate efficiency in clinical practice. We therefore report further exploratory results of an already reported dose-finding study with EPs 7630 tablets, now focussing on HRQL and PRO. A total of 406 adults with acute bronchitis were randomly assigned to one of four parallel treatment groups (placebo, 30 mg, 60 mg or 90 mg EPs 7630 daily). HRQL and PRO were assessed by questionnaires as secondary outcome measures at each study visit or daily in the patient's diary. At day 7, the patient-reported outcome measures were significantly more improved in all the three EPs 7630 groups compared to placebo (EQ-5D and EQ VAS, SF-12: physical score, impact of patient's sickness, duration of activity limitation, patient-reported treatment outcome, satisfaction with treatment). In conclusion, a statistically significant and clinically relevant improvement of HRQL/PRO compared to placebo was shown in all the three EPs 7630 groups.

Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) compared to placebo. DESIGN: Double-blind, randomized, placebo-controlled, parallel-group, multicenter trial with a group-sequential adaptive design. SUBJECTS: Patients with sinonasal symptoms of at least 7 days duration, and radiographically and clinically confirmed acute rhinosinusitis of presumably bacterial origin with a Sinusitis Severity Score (SSS) of at least 12 out of 24 points at inclusion. INTERVENTIONS: EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides (1: 8-10; extraction solvent: ethanol 11% (w/w)), or matching placebo at a dose of 60 drops three times daily for maximum 22 days. MAIN OUTCOME MEASURES: Change in the SSS after 7 days. RESULTS: 103 patients were recruited until the planned interim analysis. The mean decrease in the SSS was 5.5 points in the EPs 7630 group compared to 2.5 points in the placebo group, a difference of 3.0 points (95% confidence interval 2.0 to 3.9, p < 0.00001). This result was confirmed by all secondary parameters indicating a more favourable course of the disease and a faster recovery in the EPs 7630 group. According to the pre-specified decision rule, the study was stopped after obtaining proof of efficacy for EPs 7630. CONCLUSIONS: EPs 7630 was well tolerated and superior in efficacy compared to placebo in the treatment of acute rhinosinusitis of presumably bacterial origin.

EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomised, double-blind, placebo-controlled, multicentre trial.

Acute bronchitis commonly associated with cough is predominantly caused by viral infections. The burden on health-care systems and society is enormous. A randomised, placebo-controlled, multicentre clinical trial to investigate the efficacy and safety of a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) was conducted in 217 adult outpatients with acute bronchitis. The primary efficacy variable was the bronchitis symptom score (BSS) ranging from 0 to 20. Primary data of this study were already published in 2007. Now, we present further analyses of these already published data combined with new results in order to focus on both the most important features of acute bronchitis and pharmaco-economic aspects of the disease. The BSS decreased by 7.6 +/- 2.2 (mean +/- SD) points for the active treatment group and 5.3 +/- 3.2 points for placebo (p < 0.0001). As compared with placebo, a marked improvement has been shown for EPs 7630 for all disease symptoms (cough, sputum, rales, dyspnoe, pain on coughing, hoarseness, headache, fatigue, fever, limb pain) categorised in severity classes by the patient. Especially strong antitussive and "anti-fatigue" effects with an early onset during treatment were observed. Patients in the EPs 7630 group were sooner able to work and to a lesser extent confined to bed. In both treatment groups, 3 x 30 drops of the trial medication administered for 7 days were well tolerated. No serious adverse events have been observed. In conclusion, EPs 7630 is superior to placebo in the treatment of acute bronchitis and leads to faster remission of bronchitis related symptoms.

Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms--long-term follow-up of a placebo-controlled, double-blind, multicenter trial.

In an open-label extension of a randomized, double-blind clinical trial, the long-term efficacy and tolerability of a fixed combination of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule (PRO 160/120) were investigated in elderly men with moderate or severe lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Two hundred and fifty-seven patients were randomly treated with 2 x 1 capsule/day PRO 160/120 or placebo for 24 weeks, followed by a 24-week control period and a 48-week follow-up period in which all patients received PRO 160/120. Efficacy measures included the assessment of LUTS [International Prostate Symptom Score ((I-PSS) self-rating questionnaire] and uroflow and sonographic parameters. Two hundred and nineteen subjects participated in the follow-up. Between baseline and end of observation (week 96) the I-PSS total score was reduced by 53% (P < 0.001), peak and average urinary flow increased by 19% (P < 0.001), and residual urine volume decreased by 44% (P = 0.03). The incidence of adverse events during follow-up was one in 1,181 treatment days; in only one event a causal relationship with intake of PRO 160/120 could not be excluded. Treatment with PRO 160/120 thus provides a clinically relevant benefit over a period of 96 weeks.

Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin.

The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.

Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers.

During recent years, several case reports have been published in which the authors have voiced their suspicion of a causal relationship between hemorrhagic complications and the intake of Ginkgo biloba preparations. Therefore, a trial was conducted to investigate the influence of Ginkgo biloba special extract EGb 761 on hemostasiological parameters. Fifty healthy, male volunteers underwent 7 days of crossover treatment with 2 x 120 mg/day EGb 761 and placebo in randomized sequence. Between the two treatment phases, a washout-period of at least 3 weeks was inserted. The study's main outcome measures were bleeding time, coagulation parameters, platelet activity in response to various agonists and platelet morphology. The equivalence of the two treatments was analyzed by computing the 90% Fieller confidence intervals for the ratio between the means of the pre-post treatment differences for EGb 761 and placebo, respectively. Treatment safety was investigated by clinical laboratory and vital signs assessment and by adverse events monitoring. Among the 29 coagulation and bleeding parameters assessed, none showed any evidence of an inhibition of blood coagulation and platelet aggregation through EGb 761. Furthermore, the study did not reveal any evidence to substantiate a causal relationship between the administration of EGb 761 and hemorrhagic complications. As regards treatment tolerability, there were no interpretable differences between EGb 761 and placebo except for a slight increase of gastrointestinal complaints during administration of the herbal extract.

Software support for organ transplant management.

This paper focuses on the Organ Transplant Management (OTM) process defined as the set of activities that need to be coordinated before the surgery operation itself can take place. The main goal is to understand how the different OTM tasks are interrelated, in order to build an innovative software system that aims to support medical practitioners involved in the various decision-making steps. The current work and the extensive discussions with experts in this area provided ground for the definition of the OTM system. We argue that this tool, when integrated in real hospitals and transplant centres, will facilitate many of the tasks currently performed by humans, and will allow optimisation of precious resources such as time and personnel.