Chloride In Patients Research Articles

Once Daily Trospium Chloride is Effective and Well Tolerated for the Treatment of Overactive Bladder: Results From a Multicenter Phase III Trial

An extended release formulation of trospium chloride was recently developed for the once daily treatment of overactive bladder. We investigated the safety, efficacy and tolerability of 60 mg trospium chloride once daily. Subjects with overactive bladder were randomized 1:1 to receive 60 mg trospium chloride once daily or placebo in this 12-week multicenter, parallel, double-blind, placebo controlled trial. Primary end points were calculated changes in diary recorded daily urinary frequency and daily urgency urinary incontinence episodes. Secondary end points were urgency severity, volume voided per void and the number of urgency voids per day. Safety was assessed by clinical examination, adverse event monitoring, clinical laboratory values and resting electrocardiograms. Overall 601 subjects were prescribed trospium once daily (298) or placebo (303). Trospium once daily treatment resulted in significant improvements over placebo in all primary and key secondary efficacy outcomes at weeks 1 through 12. The most common adverse events were dry mouth (trospium 8.7% vs placebo 3%) and constipation (trospium 9.4% vs placebo 1.3%). Central nervous system adverse events were rare (headache with trospium 1.0% vs placebo 2.6%). No clinically meaningful changes in laboratory, physical examination or electrocardiogram parameters were noted. Trospium once daily provided significant improvements in overactive bladder symptoms (frequency, urgency urinary incontinence and urgency). Efficacy was similar to that seen previously with trospium chloride twice daily, while class effect anticholinergic adverse events occurred at comparatively low levels. Dry mouth was elicited at the lowest reported rate in the oral antimuscarinic drug class.

Trospium chloride in patients with neurogenic detrusor overactivity: Is dose titration of benefit to the patients?

To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

Time to onset of improvement in symptoms of overactive bladder using antimuscarinic treatment

To evaluate the time to onset of statistically significant and clinically meaningful effects of trospium chloride in patients with an overactive bladder (OAB). Data from a recent Phase III clinical study of trospium chloride were obtained, in which 658 patients with OAB were randomized (1 : 1) to placebo or trospium chloride 20 mg twice daily for 12 weeks. Original study safety endpoints consisting of adverse events, vital signs, electrocardiograms, and laboratory changes were collected, while original efficacy endpoints included number of toilet voids/day, urgency severity per toilet void, urge urinary incontinence (UUI), and volume voided per toilet void at weeks 1, 4, and 12. Results were also analysed using the OAB Symptom Composite Score (OAB-SCS). The efficacy analysis focused on changes from baseline in these endpoints from 1 to 7 days of treatment to establish the earliest point at which there was statistical significance or clinical efficacy. There were statistically significant improvements in efficacy over placebo in endpoints (toilet voids, urgency severity/void, UUI episodes, OAB-SCS) within a few days of treatment, with improvements in symptoms continuing to 7 days of treatment. There were clinically meaningful improvements in most endpoints by the end of the first week. The time to onset of the clinical effect should be studied more extensively to identify when patients might expect a clinically meaningful improvement in their OAB-related symptoms.

Multicenter phase III trial studying trospium chloride in patients with overactive bladder

Objectives To study the efficacy and safety of trospium chloride in treating overactive bladder. Trospium chloride is an anticholinergic agent with predominantly peripheral nonselective antimuscarinic activity and thus has potential therapeutic value in treating patients with overactive bladder. Methods Patients with overactive bladder were randomized on a 1:1 basis to either placebo or trospium chloride 20 mg twice daily in this 12-week, multicenter, parallel, double-blind, placebo-controlled study. The primary endpoint was the change in the average number of toilet voids per 24 hours. The secondary efficacy variables were changes in the average void urgency severity, volume per toilet void, urge frequency, number of daily urge urinary incontinence episodes, and daytime sleepiness. Results A total of 658 patients were randomized at 52 sites. Trospium chloride significantly decreased the average number of daily toilet voids, average urgency severity, urge frequency, and urge urinary incontinence episodes and increased the average volume per void at weeks 1, 4, and 12. All effects occurred by the end of week 1 and all improved and were sustained throughout the 12-week study. Adverse events included dry mouth and constipation. Conclusions Trospium chloride had significant and sustained effectiveness beginning at the end of week 1 and continuing through 12 weeks of treatment. Trospium chloride was also safe and generally well tolerated.

Do Vascular Lesions and Related Risk Factors Influence Responsiveness to Donepezil Chloride in Patients with Alzheimer’s Disease?

The purpose was to identify vascular influences on the responsiveness to donepezil chloride. The study included 50 untreated probable Alzheimer’s disease patients with the Modified Hachinski Ischemic Score <4. We assessed baseline cognitive status using the Revised Hasegawa Dementia Scale (HDS-R), Clinical Dementia Rating (CDR) and the clock drawing test (CDT). The response to 5 mg of donepezil was monitored by the CDT for 12 months. Patients were classified as true responders (TR), unchanged (UC) and non-responders according to changes on the CDT in response to treatment. High HDS-R scores, low CDT scores, low CDR and presence of hypertension (HBP) and periventricular hyperintensities (PVH) predicted a TR- or UC-type outcome. Aggravation of executive function by HBP and/or PVH and its improvement by donepezil may have been detected by the CDT.

Can Higher Doses of Oxybutynin Improve Efficacy in Neurogenic Bladder?

We evaluated the efficacy and tolerability of higher dose oxybutynin chloride in patients with neurogenic bladder and multiple sclerosis, spinal cord injury or Parkinson's disease. The study design was a prospective, 12-week dose titration trial of controlled release oxybutynin (OXY-XL). A 7-day washout period was used before initiation of the starting dose of 10 mg OXY-XL. Doses of OXY-XL were increased by 5 mg at weekly intervals to a maximum dose of 30 mg per day guided by patient perception of efficacy versus side effect. Voiding diaries were completed at baseline, and weeks 6 and 12. Post-void residuals were recorded. Criteria for study admission included post-void residual less than 200 ml. Of the 39 patients enrolled in the study 22 had multiple sclerosis, 10 had spinal cord injury and 7 had Parkinson's disease. There were 29 women (74%) and 10 men (26%). Within 1 week a decrease in the number of voids per day was seen in greater than 50% of the subjects. At the end of the study statistically significant decreases in the number of voids in 24 hours, episodes of nocturia and incontinence episodes were observed. Residual urine remained unchanged from 33.9 +/- 7.6 ml at baseline to 51.3 +/- 10.4 ml after 12 weeks at the final dose (p = 0.17). No patient experienced serious adverse events and none dropped out during the course of the 12-week study. At the end of the study 20.5% of subjects remained on 30 mg, 15.4% on 25 mg, 23.1% on 20 mg, 15.4% on 15 mg and 25.6% on 10 mg OXY-XL. Aggressive dosing of OXY-XL is safe and effective in patients with neurogenic bladder. Compared with nonneurogenic overactive bladder, higher doses of OXY-XL (15 mg daily or greater) were requested by 74.4% of the patients in our study. The onset of clinical efficacy can occur within 1 week, and doses up to 30 mg are well tolerated and effective in this population.

Trospium chloride in patients with detrusor overactivity

Trospium chloride in patients with detrusor overactivity

Randomised, Double-Blind, Placebo-Controlled Study on the Efficacy and Tolerance of Trospium Chloride in Patients with Motor Urge Incontinence

Objective Trospium chloride is an antimuscarinic drug with a quaternary ammonium structure for the treatment of detrusor instability and hyper-reflexia. It is generally considered to be well tolerated, but exhibits poor gastrointestinal absorption after oral administration. This study was conducted to assess the efficacy and safety of trospium chloride 15mg three times daily for 28 days in patients with motor urge incontinence.

Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomised, double-blind, multicentre clinical trial.

Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomised, double-blind, multicentre clinical trial.

INTERSTITIAL CYSTITIS: BLADDER TRAINING WITH INTRAVESICAL OXYBUTYNIN

We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis. The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis. Patients were treated with gradual intravesical instillation of saline oxybutynin solution (oxybutynin group) or gradual filling of simple saline (control group). Evaluation parameters consisted of symptom problem index, voids per day, volume per void, functional bladder capacity, volume at first sensation, cystometric bladder capacity and cystometric volume at first sensation. Statistically significant improvement of all evaluated parameters was found in both groups. When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group. Bladder training alone produces a satisfactory result by gradually expanding the bladder, and an additional statistically significant improvement is evident with intravesical oxybutynin.

Effect of manidipine chloride on various aspects of endocrine function, including plasma levels of endothelin-1 and human atrial natriuretic peptide, in patients with essential hypertension

We assessed various aspects of endocrine function in patients treated for essential hypertension with manidipine chloride, a calcium channel blocker, to study the effects of this drug on several endogenous humoral factors, including human atrial natriuretic peptide (hANP) and endothelin-1 which influence vasoconstriction and blood fluid volume. The study included 19 patients with essential hypertension. All patients received manidipine chloride 10 mg/d for 24 weeks. After treatment blood pressure was normalized in all patients, and there were no significant changes in plasma renin activity or blood concentrations, adrenaline, or noradrenaline. There was a statistically significant negative correlation between the change in ET levels and hANP levels before and after treatment. We also observed a statistically significant negative correlation between the change in systolic blood pressure caused by manidipine chloride and the change in hANP levels before and after treatment. These findings suggest that hANP and ET levels are systematically changed by manidipine chloride in patients with essential hypertension. We also speculate that changes in blood pressure may be closely related to levels of hANP in patients treated with manidipine chloride.

Contact allergies to nickel sulfate, gold sodium thiosulfate and palladium chloride in patients claiming side-effects from dental alloy components.

397 patients claiming various subjective symptoms related to dental restoration materials have been tested for the presence of metal allergy. The resultant data have been compared with the corresponding allergies of eczematous patients. The frequency difference of metal allergy in the dental group is statistically significant or close to significance for nickel sulfate, potassium dichromate, cobalt chloride, palladium chloride and gold sodium thiosulfate. The findings suggest that the dental patient group represents a subgroup with a high frequency of metal allergy.

Continuous Infusion of Mivacurium Chloride in Patients with Varying Renal Function

Continuous Infusion of Mivacurium Chloride in Patients with Varying Renal Function

Mivacurium Chloride in Patients with Chronic Renal Failure

Mivacurium Chloride in Patients with Chronic Renal Failure

Haemodynamic comparison of protamine sulphate and chloride in patients with normal left ventricular function undergoing coronary bypass surgery

Haemodynamic comparison of protamine sulphate and chloride in patients with normal left ventricular function undergoing coronary bypass surgery

Pharmacokinetic studies of ambenonium chloride in patients with myasthenia gravis

Serum levels of ambenonium chloride (AC) were monitored in 4 myasthenic patients. This determination revealed important intraindividual variations (up to 10-fold) over a period of 24 h. Levels varied considerably between different patients (maximum serum concentration of ambenonium chloride ranged from 0.129 to 0.812 micrograms/ml) and no correlation between the daily dose and the AUC was found. These characteristic properties of ambenonium chloride could explain the erratic pattern of bioavailability observed as well as the difficulty in controlling the disease in some patients.

Water and electrolyte balance after ileoanal anastomosis

Water and electrolyte balance was studied in 30 patients with ileoanal anastomosis and J pouch, 10 patients with conventional ileostomy, and nine nonoperated patients with quiescent ulcerative colitis. Serum electrolyte concentrations, daily urinary volume, and daily losses of sodium, potassium, and chloride were measured in all patients. Daily fecal weight and daily losses of sodium and potassium were analyzed in patients with ileoanal anastomosis or conventional ileostomy. Serum chloride in patients with ileoanal anastomosis was significantly lower (P less than 0.05) than in those with conventional ileostomy or in nonoperated patients. Daily urinary loss of sodium in nonoperated patients was significantly higher than in patients with ileoanal anastomosis (P less than 0.01) or conventional ileostomy (P less than 0.05). Daily urinary loss of chloride in patients with ileoanal anastomosis was significantly lower (P less than 0.05) than in nonoperated patients. Daily fecal loss of potassium in patients with ileoanal anastomosis was significantly higher (P less than 0.05) than in those with conventional ileostomy. Daily urinary volume and fecal weight did not differ significantly in patients with ileoanal anastomosis or conventional ileostomy. The present study indicates that changes in water and sodium balance after ileoanal anastomosis are similar to those after conventional ileostomy but chloride balance is more altered after ileoanal anastomosis.

Increased Dietary Sodium Chloride in Patients Treated with Antihypertensive Drugs

Eleven patients on a normal diet with mild to moderate essential hypertension satisfactorily treated with diverse hypotensive agents entered a randomized double-blind cross-over study to evaluate the effect of additional sodium chloride (100 mmol slow sodium) compared with placebo on blood pressure control over a 6 week period. Despite excellent tablet compliance, sodium chloride failed to significantly alter mean supine or erect blood pressure. These findings as well as a review of the relevant literature suggest that excess dietary sodium does not jeopardize blood pressure control in such patients.

Ambulant Monitoring to Assess the Efficacy of Oxybutynin Chloride in Patients with Mixed Incontinence

Objective parameters show the efficacy of oxybutynin chloride on uninhibited detrusor behavior. In the 24-hour ambulant monitoring method, intravesical and abdominal pressure are recorded. This enables quantification of the amplitude, duration, and frequency of uninhibited detrusor contractions. It is even possible to show the efficacy of this drug objectively in patients with severe mixed incontinence.

Cardiovascular Effects of Mivacurium Chloride in Patients with Coronary Artery Disease

Cardiovascular Effects of Mivacurium Chloride in Patients with Coronary Artery Disease